Potential disease targets for drugs that disrupt protein - Protein interactions of Grb2 and Crk family adaptors

Current Pharmaceutical Design

Volumn 12, Issue 5, 2006, Pages 529-548

  Feller, Stephan M ^a   Lewitzky, Marc ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Adaptor proteins; Cancer; Cell signalling; Crk; Grb2; Inhibitor development; Mona Gads

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; ABELSON KINASE; ADAPTOR PROTEIN; CRK LIKE PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 1B; DOCKING PROTEIN; GEFITINIB; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; IMATINIB; PAXILLIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOTRANSFERASE; PROTEIN INHIBITOR; RAF PROTEIN; RAS PROTEIN; RECEPTOR; SORAFENIB; ONCOPROTEIN;

CLINICAL TRIAL; DRUG MECHANISM; DRUG TARGETING; GENE DISRUPTION; HUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; SRC HOMOLOGY DOMAIN; ANIMAL; CHEMICAL STRUCTURE; DRUG EFFECT;

ANIMALS; GRB2 ADAPTOR PROTEIN; HUMANS; MODELS, MOLECULAR; PROTO-ONCOGENE PROTEINS C-CRK; SRC HOMOLOGY DOMAINS;

EID: 33644925547     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161206775474369     Document Type: Review

References (387)

1. Kuriyan J, Cowburn D. Modular peptide recognition domains in eukaryotic signaling. Annu Rev Biophys Biomol Struct 1997; 26: 259-88.
2. Pawson T, Scott JD. Signaling through scaffold, anchoring, and adaptor proteins. Science 1997; 278: 2075-80.
3. Pawson T. Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems. Cell 2004; 116: 191-203.
4. Buday L. Membrane-targeting of signalling molecules by SH2/SH3 domain-containing adaptor proteins. Biochim Biophys Acta 1999; 1422: 187-204.
5. Mayer BJ. SH3 domains: complexity in moderation. J Cell Sci 2001; 114: 1253-63.
6. Musacchio A. How SH3 domains recognize proline. Adv Protein Chem 2002; 61: 211-68.
7. Zarrinpar A, Bhattacharyya RP, Lim WA. The structure and function of proline recognition domains. Sci STKE 2003; 2003: RE8.
8. Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, et al. SH2 domains recognize specific phosphopeptide sequences. Cell 1993; 72: 767-78.
9. Songyang Z, Shoelson SE, McGlade J, Olivier P, Pawson T, Bustelo XR, et al. Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol 1994; 14: 2777-85.
10. Rahuel J, Gay B, Erdmann D, Strauss A, Garcia-Echeverria C, Furet P, et al. Structural basis for specificity of Grb2-SH2 revealed by a novel ligand binding mode. Nat Struct Biol 1996; 3: 586-9.
11. Cho S, Velikovsky CA, Swaminathan CP, Houtman JC, Samelson LE, Mariuzza RA. Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads. EMBO J 2004; 23: 1441-51.
12. Cody WL, Lin Z, Panek RL, Rose DW, Rubin JR. Progress in the development of inhibitors of SH2 domains. Curr Pharm Des 2000; 6: 59-98.
13. Fretz H, Furet P, Garcia-Echeverria C, Schoepfer J, Rahuel J. Structure-based design of compounds inhibiting Grb2-SH2 mediated protein-protein interactions in signal transduction pathways. Curr Pharm Des 2000; 6: 1777-96.
14. Vidal M, Gigoux. V, Garbay C. SH2 and SH3 domains as targets for anti-proliferative agents. Crit Rev Oncol Hematol 2001; 40: 175-86.
15. Garcia-Echeverria C. Antagonists of the Src homology 2 (SH2) domains of Grb2, Src, Lck and ZAP-70. Curr Med Chem 2001; 8: 589-604.
16. Shakespeare WC. SH2 domain inhibition: a problem solved? Curr Opin Chem Biol 2001; 5: 409-15.
17. Sawyer TK, Bohacek RS, Dalgarno DC, Eyermann CJ, Kawahata N, Metcalf CA 3rd, et al. SRC homology-2 inhibitors: peptidomimetic and nonpeptide. Mini Rev Med Chem 2002; 2: 475-88.
18. Burke TR Jr, Lee K. Phosphotyrosyl mimetics in the development of signal transduction inhibitors. Acc Chem Res 2003; 36: 426-33.
19. Forman-Kay JD, Pawson T. Diversity in protein recognition by PTB domains. Curr Opin Struct Biol 1999; 9: 690-5.
20. Yaffe MB, Elia AE. Phosphoserine/threonine-binding domains. Curr Opin Cell Biol 2001; 13: 131-8.
21. Manke LA, Lowery DM, Nguyen A, Yaffe MB. BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 2003; 302: 636-9.
22. Yu X, Chini CC, He M, Mer G, Chen J. The BRCT domain is a phospho-protein binding domain. Science 2003; 302: 639-42.
23. Rodriguez M, Yu X, Chen J, Songyang Z. Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. J Biol Chem 2003; 278: 52914-8.
24. Stoll R, Renner C, Zweckstetter M, Bruggert M, Ambrosius D, Palme S, et al. The extracellular human melanoma inhibitory activity (MIA) protein adopts an SH3 domain-like fold. EMBO J 2001; 20: 340-9.
25. Lougheed JC, Holton JM, Alber T, Bazan JF, Handel TM. Structure of melanoma inhibitory activity protein, a member of a recently identified family of secreted proteins. Proc Natl Acad Sci USA 2001; 98: 5515-20.
26. Stoll R, Renner C, Buettner R, Voelter W, Bosserhoff AK, Holak TA. Backbone dynamics of the human MIA protein studied by (15)N NMR relaxation: implications for extended interactions of SH3 domains. Protein Sci 2003; 12: 510-9.
27. Lodi PJ, Ernst JA, Kuszewski J, Hickman AB, Engelman A, Craigie R, et al. Solution structure of the DNA binding domain of HIV-1 integrase. Biochemistry 1995; 34: 9826-33.
28. Eijkelenboom AP, Lutzke RA, Boelens R, Plasterk RH, Kaptein R, Hard K. The DNA-binding domain of HIV-1 integrase has an SH3-like fold. Nat Struct Biol 1995; 2: 807-10.
29. Nakagawa A, Nakashima T, Taniguchi M, Hosaka H, Kimura M, Tanaka I. The three-dimensional structure of the RNA-binding domain of ribosomal protein L2; a protein at the peptidyl transferase center of the ribosome. EMBO J 1999; 18: 1459-67.
30. Ponting CP, Aravind L, Schultz J, Bork P, Koonin EV. Eukaryotic signalling domain homologues in archaea and bacteria. Ancient ancestry and horizontal gene transfer. J Mol Biol 1999; 289: 729-45.
31. Whisstock JC, Lesk AM. SH3 domains in prokaryotes. Trends Biochem Sci 1999; 24: 132-3.
32. Bakal CJ, Davies JE. No longer an exclusive club: eukaryotic signalling domains in bacteria. Trends Cell Biol 2000; 10: 32-8.
33. Agrawal V, Kishan RK. Functional evolution of two subtly different (similar) folds. BMC Struct Biol 200 1; 1: 5.
34. Anantharaman V, Aravind L. The PRC-barrel: a widespread, conserved domain shared by photosynthetic reaction center subunits and proteins of RNA metabolism. Genome Biol 2002; 3: research0061.1-9.
35. Berry DM, Nash P, Liu SK, Pawson T, McGlade CJ. A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling. Curr Biol 2002; 12: 1336-41.
36. Liu Q, Berry D, Nash P, Pawson T, McGlade CJ, Li SS. Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition. Mol Cell 2003; 11: 471-81.
37. Harkiolaki M, Lewitzky M, Gilbert RJ, Jones EY, Bourette RP, Mouchiroud G, et al. Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76. EMBO J 2003; 22: 2571-82.
38. Cussac D, Vidal M, Leprince C, Liu WQ, Cornille F, Tiraboschi G, et al. A Sos-derived peptidimer blocks the Ras signaling pathway by binding both Grb2 SH3 domains and displays antiproliferative activity. FASEB J 1999; 13: 31-8.
39. Kardinal C, Posern G, Zheng J, Knudsen BS, Amgen Peptide Technology Group, Moarefi I, et al. Rational development of cell-penetrating high affinity SH3 domain binding peptides that selectively disrupt the signal transduction of Crk family adapters. Ann N Y Acad Sci 1999; 886: 289-92.
40. Wang J, Dai H, Yousaf N, Moussaif M, Deng Y, Boufelliga A, et al. Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Mol Cell Biol 1999; 19: 6217-28.
41. Kardinal C, Konkol B, Schulz A, Posern G, Lin H, Adermann K, et al. Cell-penetrating SH3 domain blocker peptides inhibit proliferation of primary blast cells from CML patients. FASEB J 2000; 14: 1529-38.
42. Riedel H, Yousaf N, Zhao Y, Dai H, Deng Y, Wang J. PSM, a mediator of PDGF-BB-, IGF-I-, and insulin-stimulated mitogenesis. Oncogene 2000; 19: 39-50.
43. Kardinal C, Konkol B, Lin H, Eulitz M, Schmidt EK, Estrov Z, et al. Chronic myelogenous leukemia blast cell proliferation is inhibited by peptides that disrupt Grb2-SoS complexes. Blood 2001; 98: 1773-81.
44. Kiosses WB, Hood J, Yang S, Gerritsen ME, Cheresh DA, Alderson N, et al. A dominant-negative p65 PAK peptide inhibits angiogenesis. Circ Res 2002; 90: 697-702.
45. Puto LA, Pestonjamasp K, King CC, Bokoch GM. p21 -activated kinase 1 (PAK1) interacts with the Grb2 adapter protein to couple to growth factor signaling. J Biol Chem 2003; 278: 9388-93.
46. Pisabarro MT, Serrano L. Rational design of specific high-affinity peptide ligands for the Abl-SH3 domain. Biochemistry 1996; 35: 10634-40.
47. Grabs D, Slepnev VI, Songyang Z, David C, Lynch M, Cantley LC, et al. The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence. J Biol Chem 1997; 272: 13419-25.
48. Manser E, Loo TH, Koh CG, Zhao ZS, Chen XQ, Tan L, et al. PAK kinases are directly coupled to the PIX family of nucleotide exchange factors. Mol Cell 1998; 1: 183-92.
49. Sharma SV, Oneyama C, Yamashita Y, Nakano H, Sugawara K, Hamada M, et al. UCS 15A, a non-kinase inhibitor of Src signal transduction. Oncogene 2001; 20: 2068-79.
50. Oneyama C, Nakano H, Sharma SV. UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug. Oncogene 2002; 21: 2037-50.
51. Oneyama C, Agatsuma T, Kanda Y, Nakano H, Sharma SV, Nakano S, et al. Synthetic inhibitors of proline-rich ligand-mediated protein-protein interaction: potent analogs of UCS15A. Chem Biol 2003; 10: 443-51.
52. Lewitzky M, Harkiolaki M, Domart MC, Jones EY, Feller SM. Mona/Gads SH3C Binding to Hematopoietic Progenitor Kinase 1 (HPK1) Combines an Atypical SH3 Binding Motif, R/KXXK, with a Classical PXXP Motif Embedded in a Polyproline Type II (PPII) Helix. J Biol Chem 2004; 279: 28724-28732.
53. Mayer BJ, Hamaguchi M, Hanafusa H. A novel viral oncogene with structural similarity to phospholipase C. Nature 1988; 332: 272-5.
54. Tsuchie H, Chang CH, Yoshida M, Vogt PK. A newly isolated avian sarcoma virus, ASV-1, carries the crk oncogene. Oncogene 1989; 4: 1281-4.
55. Matsuda M, Tanaka S, Nagata S, Kojima A, Kurata T, Shibuya M. Two species of human CRK cDNA encode proteins with distinct biological activities. Mol Cell Biol 1992; 12: 3482-9.
56. Reichman CT, Mayer BJ, Keshav S, Hanafusa H. The product of the cellular crk gene consists primarily of SH2 and SH3 regions. Cell Growth Differ 1992; 3: 451-60.
57. Sabe H, Okada M, Nakagawa H, Hanafusa H. Activation of c-Src in cells bearing v-Crk and its suppression by Csk. Mol Cell Biol 1992; 12: 4706-13.
58. Feller SM, Knudsen B, Hanafusa H. c-Abl kinase regulates the protein binding activity of c-Crk. EMBO J 1994; 13: 2341-51.
59. Sabe H, Shoelson SE, Hanafusa H. Possible v-Crk-induced transformation through activation of Src kinases. J Biol Chem 1995; 270: 31219-24.
60. Greulich H, Hanafusa H. A role for Ras in v-Crk transformation. Cell Growth Differ 1996; 7: 1443-51.
61. Tanaka S, Ouchi T, Hanafusa H. Downstream of Crk adaptor signaling pathway: activation of Jun kinase by v-Crk through the guanine nucleotide exchange protein C3G. Proc Natl Acad Sci U S A 1997; 94: 2356-61.
62. Mochizuki N, Ohba Y, Kobayashi S, Otsuka N, Graybiel AM, Tanaka S, et al. Crk activation of JNK via C3G and R-Ras. J Biol Chem 2000; 275: 12667-71.
63. Liu E, Thant AA, Kikkawa. F, Kurata H, Tanaka S, Nawa A, et al. The Ras-mitogen-activated protein kinase pathway is critical for the activation of matrix metalloproteinase secretion and the invasiveness in v-crk-transformed 3Y1. Cancer Res 2000; 60: 2361-4.
64. Akagi T, Murata K, Shishido T, Hanafusa H. v-Crk activates the phosphoinosifide 3-kinase/AKT pathway by utilizing focal adhesion kinase and H-Ras. Mol Cell Biol 2002; 22: 7015-23.
65. Oehrl W, Kardinal C, Ruf S, Adermann K, Groffen J, Feng GS, et al. The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins. Oncogene 1998; 17: 1893-901.
66. Imaizumi T, Araki K, Miura K, Araki M, Suzuki M, Terasaki H, et al. Mutant mice lacking Crk-II caused by the gene trap insertional mutagenesis: Crk-II is not essential for embryonic development. Biochem Biophys Res Commun 1999; 266: 569-74.
67. Kiyokawa E, Mochizuki N, Kurata T, Matsuda M. Role of Crk oncogene product in physiologic signaling. Crit Rev Oncog 1997; 8: 329-42.
68. Feller SM, Posern G, Voss J, Kardinal C, Sakkab D, Zheng J, et al. Physiological signals and oncogenesis mediated through Crk family adapter proteins. J Cell Physiol 1998; 177: 535-52.
69. Feller SM. Crk family adaptors-signalling complex formation and biological roles. Oncogene 2001; 20: 6348-71.
70. Nishihara H, Tanaka S, Tsuda M, Oikawa S, Maeda M, Shimizu M, et al. Molecular and immumohistochemical analysis of signaling adaptor protein Crk in human cancers. Cancer Lett 2002; 180: 55-61.
71. Iwahara T, Akagi T, Shishido T, Hanafusa H. CrkII induces serum response factor activation and cellular transformation through its function in Rho activation. Oncogene 2003; 22: 5946-57.
72. Burton EA, Plattner R, Pendergast AM. Abl tyrosine kinases are required for infection by Shigella flexneri. EMBO J 2003; 22: 5471-9.
73. Prosser S, Sorokina E, Pratt P, Sorokin A. CrkIII: a novel and biologically distinct member of the Crk family of adaptor proteins. Oncogene 2003; 22: 4799-806.
74. ten Hoeve J, Morris C, Heisterkamp N, Groffen J. Isolation and chromosomal localization of CRKL, a human crk-like gene. Oncogene 1993; 8: 2469-74.
75. Nichols GL, Raines MA, Vera JC, Lacomis L, Tempst P, Golde DW. Identification of CRKL as the constitutively phosphorylated 39-kD tyrosine phosphoprotein in chronic myelogenous leukemia cells. Blood 1994; 84: 2912-8.
76. Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD, Druker BJ. Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia. J Biol Chem 1994; 269: 22925-8.
77. ten Hoeve J, Arlinghaus RB, Guo JQ, Heisterkamp N, Groffen J. Tyrosine phosphorylation of CRKL in Philadelphia+ leukemia. Blood 1994; 84: 1731-6.
78. de Jong R, Haataja L, Voncken JW, Heisterkamp N, Groffen J. Tyrosine phosphorylation of murine Crkl. Oncogene 1995; 11: 1469-74.
79. Voss J, Posern G, Hannemann JR, Wiedemann LM, Turhan AG, Poirel H, et al. The leukaemic oncoproteins Bcr-Abl and Tel-Abl (ETV6/Abl) have altered substrate preferences and activate similar intracellular signalling pathways. Oncogene 2000; 19: 1684-90.
80. ten Hoeve J, Kaartinen V, Fioretos T, Haataja L, Voncken JW, Heisterkamp N, et al. Cellular interactions of CRKL, and SH2-SH3 adaptor protein. Cancer Res 1994; 54: 2563-7.
81. Hemmeryckx B, van Wijk A, Reichert A, Kaartinen V, de Jong R, Pattengale PK, et al. Crkl enhances leukemogenesis in BCR/ABL P190 transgenic mice. Cancer Res 2001; 61: 1398-405.
82. Senechal K, Halpern J, Sawyers CL. The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene. J Biol Chem 1996; 271: 23255-61.
83. de Jong R, ten Hoeve J, Heisterkamp N, Groffen J. Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site. Oncogene 1997; 14: 507-13.
84. Senechal K, Heaney C, Druker B, Sawyers CL. Structural requirements for function of the Crkl adapter protein in fibroblasts and hematopoietic cells. Mol Cell Biol 1998; 18: 5082-90.
85. Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, et al. Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood 1997; 89: 297-306.
86. Hemmeryckx B, Reichert A, Watanabe M, Kaartinen V, de Jong R, Pattengale PK, et al. BCR/ABL P190 transgenic mice develop leukemia in the absence of Crkl. Oncogene 2002; 21: 3225-31.
87. Capdeville R, Buchdunger E, Zimmermann J, Matter A. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 2002; 1: 493-502.
88. Mauro MJ, O'Dwyer M, Heinrich MC, Druker BJ. STI571: a paradigm of new agents for cancer therapeutics. J Clin Oncol 2002; 20: 325-34.
89. Savage DG, Antman KH. Imatinib mesylate - a new oral targeted therapy. N Engl J Med 2002; 346: 683-93.
90. Goldman JM, Melo JV. Chronic myeloid leukemia - advances in biology and new approaches to treatment. N Engl J Med 2003; 349: 1451-64.
91. Sawyers CL. Opportunities and challenges in the development of kinase inhibitor therapy for cancer. Genes Dev 2003; 17: 2998-3010.
92. Gambacorti-Passerini CB, Gunby RH, Piazza R, Galietta A, Rostagno R, Scapozza L. Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias. Lancet Oncol 2003; 4: 75-85.
93. Azam M, Latek RR, Daley GQ. Mechanisms of autoinhibition and STI-571/ imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 2003; 112: 831-43.
94. Goldman JM. Chronic myeloid leukemia-still a few questions. Exp Hematol 2004; 32: 2-10.
95. Schwartzberg PL, Stall AM, Hardin JD, Bowdish KS, Humaran T, Boast S, et al. Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populations. Cell 1991; 65: 1165-75.
96. Tybulewicz VL, Crawford CE, Jackson PK, Bronson RT, Mulligan RC. Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell 1991; 65: 1153-63.
97. Hardin JD, Boast S, Schwartzberg PL, Lee G, Alt FW, Stall AM, et al. Bone marrow B lymphocyte development in c-abl-deficient mice. Cell Immunol 1995; 165: 44-54.
98. Koleske AJ, Gifford AM, Scott ML, Nee M, Bronson RT, Miczek KA, et al. Essential roles for the Abl and Arg tyrosine kinases in neurulation. Neuron 1998; 21: 1259-72.
99. Kain KH, Klemke RL. Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes. J Biol Chem 2001; 276: 16185-92.
100. Guris DL, Fantes J, Tara D, Druker BJ, Imamoto A. Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nat Genet 2001; 27: 293-8.
101. Li L, Guris DL, Okura M, Imamoto A. Translocation of CrkL to focal adhesions mediates integrin-induced migration downstream of Src family kinases. Mol Cell Biol 2003; 23: 2883-92.
102. Peterson AC, Marks RE, Fields PE, Imamoto A, Gajewski TF. T cell development and function in CrkL-deficient mice. Eur J Immunol 2003; 33: 2687-95.
103. Rosen MK, Yamazaki T, Gish GD, Kay CM, Pawson T, Kay LE. Direct demonstration of an intramolecular SH2-phosphotyrosine interaction in the Crk protein. Nature 1995; 374: 477-9.
104. Koval AP, Blakesley VA, Roberts CT Jr, Zick Y, Leroith D. Interaction in vitro of the product of the c-Crk-II proto-oncogene with the insulin-like growth factor I receptor. Biochem J 1998; 330: 923-32.
105. Okada S, Matsuda M, Anafi M, Pawson T, Pessin JE. Insulin regulates the dynamic balance between Ras and Rap1 signaling by coordinating the assembly states of the Grb2-SOS and CrkII-C3G complexes. EMBO J 1998; 17: 2554-65.
106. Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, et al. Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor. J Biol Chem 1998; 273: 17186-91.
107. Matsumoto T, Yokote K, Take A, Takemoto M, Asaumi S, Hashimoto Y, et al. Differential interaction of CrkII adaptor protein with platelet-derived growth factor alpha- and beta-receptors is determined by its internal tyrosine phosphorylation. Biochem Biophys Res Commun 2000; 270: 28-33.
108. Escalante M, Courtney J, Chin WG, Teng KK, Kim JI, Fajardo JE, et al. Phosphorylation of c-Crk II on the negative regulatory Tyr222 mediates nerve growth factor-induced cell spreading and morphogenesis. J Biol Chem 2000; 275: 24787-97.
109. Jin S, Zhai B, Qiu Z, Wu J, Lane MD, Liao K. c-Crk, a substrate of the insulin-like growth factor-1 receptor tyrosine kinase, functions as an early signal mediator in the adipocyte differentiation process. J Biol Chem 2000; 275: 34344-52.
110. Zvara A, Fajardo JE, Escalante M, Cotton G, Muir T, Kirsch KH, et al. Activation of the focal adhesion kinase signaling pathway by structural alterations in the carboxyl-terminal region of c-Crk II. Oncogene 2001; 20: 951-61.
111. Shishido T, Akagi T, Chalmers A, Maeda M, Terada T, Georgescu MM, et al. Crk family adaptor proteins trans-activate c-Abl kinase. Genes Cells 2001; 6: 431-40.
112. Kurokawa K, Mochizuki N, Ohba Y, Mizuno H, Miyawaki A, Matsuda M. A pair of fluorescent resonance energy transferbased probes for tyrosine phosphorylation of the CrkII adaptor protein in vivo. J Biol Chem 2001; 276: 31305-10.
113. Abassi YA, Vuori K. Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling. EMBO J 2002; 21: 4571-82.
114. Takino T, Tamura M, Miyamori H, Araki M, Matsumoto K, Sato H, et al. Tyrosine phosphorylation of the CrkII adaptor protein modulates cell migration. J Cell Sci 2003; 116: 3145-55.
115. Kain KH, Gooch S, Klemke RL. Cytoplasmic c-Abl provides a molecular 'Rheostat' controlling carcinoma cell survival and invasion. Oncogene 2003; 22: 6071-80.
116. Martin GS. The hunting of the Src. Nat Rev Mol Cell Biol 2001; 2: 467-75.
117. de Jong R, van Wijk A, Heisterkamp N, Groffen J. C3G is tyrosine-phosphorylated after integrin-mediated cell adhesion in normal but not in Bcr/Abl expressing cells. Oncogene 1998; 17: 2805-10.
118. Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Mano H, et al. A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner. EMBO J 1994; 13: 3748-56.
119. Nojima Y, Mimura T, Morino N, Hamasaki K, Furuya H, Sakai R, et al. Tyrosine phosphorylation of p130Cas in cell adhesion and transformation. Hum Cell 1996; 9: 169-74.
120. O'Neill GM, Fashena SJ, Golemis EA. Integrin signalling: a new Cas(t) of characters enters the stage. Trends Cell Biol 2000; 10: 111-9.
121. Bouton AH, Riggins RB, Bruce-Staskal PJ. Functions of the adapter protein Cas: signal convergence and the determination of cellular responses. Oncogene 2001; 20: 6448-58.
122. Alexandropoulos K, Donlin LT, Xing L, Regelmann AG. Sin: good or bad? A T lymphocyte perspective. Immunol Rev 2003; 192: 181-95.
123. Mayer BJ, Hirai H, Sakai R. Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases. Curr Biol 1995; 5: 296-305.
124. Honda H, Oda H, Nakamoto T, Honda Z, Sakai R, Suzuki T, et al. Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas. Nat Genet 1998; 19: 361-5.
125. Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA. CAS/Crk coupling serves as a "molecular switch" for induction of cell migration. J Cell Biol 1998; 140: 961-72.
126. Hsia DA, Mitra SK, Hauck CR, Streblow DN, Nelson JA, Ilic D, et al. Differential regulation of cell motility and invasion by FAK. J Cell Biol 2003; 160: 753-67.
127. Brinkman A, van der Flier S, Kok EM, Dorssers LC. BCAR1, a human homologue of the adapter protein p130Cas, and antiestrogen resistance in breast cancer cells. J Natl Cancer Inst 2000; 92: 112-20.
128. van der Flier S, Brinkman A, Look MP, Kok EM, Meijer-van Gelder ME, Klijn JG, et al. Bcar1/p130Cas protein and primary breast cancer: prognosis and response to tamoxifen treatment. J Natl Cancer Inst 2000; 92: 120-7.
129. Grebenchtchikov N, Brinkman A, Van Broekhoven SP, De Jong D, Geurts-Moespot A, Span PN, et al. Development of an ELISA for Measurement of BCAR1 Protein in Human Breast Cancer Tissue. Clin Chem 2004; 50: 1356-63.
130. Dorssers LC, Grebenchtchikov N, Brinkman A, Lock MP, van Broekhoven SPJ, de Jong D, et al. The prognostic value of BCAR1 in patients with primary breast cancer. Clin Cancer Res 2004; 10: 6194-202.
131. Gotoh T, Cai D, Tian X, Feig LA, Lerner A. p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor. J Biol Chem 2000; 275: 30118-23.
132. Cai D, Iyer A, Felekkis KN, Near RI, Luo Z, Chernoff J, et al. AND-34/ BCAR3, a GDP exchange factor whose overexpression confers antiestrogen resistance, activates Rac, PAK1, and the cyclin D1 promoter. Cancer Res 2003; 63: 6802-8.
133. Dorssers LC, Veldscholte J. Identification of a novel breast-cancer-anti-estrogen-resistance (BCAR2) locus by cell-fusion-mediated gene transfer in human breast-cancer cells. Int J Cancer 1997; 72: 700-5.
134. Turner CE. Paxillin and focal adhesion signalling. Nat Cell Biol 2000; 2: E231-6.
135. Schaller MD. Paxillin: a focal adhesion-associated adaptor protein. Oncogene 2001; 20: 6459-72.
136. Sattler M, Pisick E, Morrison PT, Salgia R. Role of the cytoskeletal protein paxillin in oncogenesis. Crit Rev Oncog 2000; 11: 63-76.
137. Ma PC, Maulik G, Christensen J, Salgia R. c-Met: structure, functions and potential for therapeutic inhibition. Cancer Metastasis Rev 2003; 22: 309-25.
138. Giannone G, Dubin-Thaler BJ, Dobereiner HG, Kieffer N, Bresnick AR, Sheetz MP. Periodic lamellipodial contractions correlate with rearward actin waves. Cell 2004; 116: 431-43.
139. Turner CE, Brown MC, Perrotta JA, Riedy MC, Nikolopoulos SN, McDonald AR, et al. Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling. J Cell Biol 1999; 145: 851-63.
140. Kissil JL, Wilker EW, Johnson KC, Eckman MS, Yaffe MB, Jacks T. Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol Cell 2003; 12: 841-9.
141. Schaller MD, Schaefer EM. Multiple stimuli induce tyrosine phosphorylation of the Crk-binding sites of paxillin. Biochem J 2001; 360: 57-66.
142. Hagel M, George EL, Kim A, Tamimi R, Opitz SL, Turner CE, et al. The adaptor protein paxillin is essential for normal development in the mouse and is a critical transducer of fibronectin signaling. Mol Cell Biol 2002; 22: 901-15.
143. Wade R, Bohl J, Vande Pol S. Paxillin null embryonic stem cells are impaired in cell spreading and tyrosine phosphorylation of focal adhesion kinase. Oncogene 2002; 21: 96-107.
144. Stuart KA, Riordan SM, Lidder S, Crostella L, Williams R, Skouteris GG. Hepatocyte growth factor/scatter factor-induced intracellular signalling. Int J Exp Pathol 2000; 81: 17-30.
145. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol 2003; 4: 915-25.
146. Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, et al. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 2003; 63: 6272-81.
147. Romano A, Wong WT, Santoro M, Wirth PJ, Thorgeirsson SS, Di Fiore PP. The high transforming potency of erbB-2 and ret is associated with phosphorylation of paxillin and a 23 kDa protein. Oncogene 1994; 9: 2923-33.
148. Vadlamudi R, Adam L, Tseng B, Costa L, Kumar R. Transcriptional up-regulation of paxillin expression by heregulin in human breast cancer cells. Cancer Res 1999; 59: 2843-6a
149. Bocciardi R, Mograbi B, Pasini B, Borrello MG, Pierotti MA, Bourget I, et al. The multiple endocrine neoplasia type 2B point mutation switches the specificity of the Ret tyrosine kinase towards cellular substrates that are susceptible to interact with Crk and Nck. Oncogene 1997; 15: 2257-65.
150. Furge KA, Zhang YW, Vande Woude GF. Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene 2000; 19: 5582-9.
151. Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, et al. Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. J Biol Chem 2000; 275: 10772-8.
152. Wolf I, Jenkins BJ, Liu Y, Seiffert M, Custodio JM, Young P, et al. Gab3, a new DOS/Gab family member, facilitates macrophage differentiation. Mol Cell Biol 2002; 22: 231-44.
153. Garcia-Guzman M, Dolfi F, Zeh K, Vuori K. Met-induced JNK activation is mediated by the adapter protein Crk and correlates with the Gab1 - Crk signaling complex formation. Oncogene 1999; 18: 7775-86.
154. Sakkab D, Kardinal C, Lewitzky M, Walburg M, Knudsen B, Feller S. Hepatocyte growth factor/scatter factor (HGF) signaling depends on Crk family adapter proteins. Signal Transduction 2001; 1: 25-36.
155. Sachs M, Brohmann H, Zechner D, Muller T, Hulsken J, Walther I, et al. Essential role of Gab1 for signaling by the c-Met receptor in vivo. J Cell Biol 2000; 150: 1375-84.
156. Gu H, Neel BG. The "Gab" in signal transduction. Trends Cell Biol 2003; 13: 122-30.
157. Liu Y, Rohrschneider LR. The gift of Gab. FEBS Lett 2002; 515: 1-7.
158. Nishida K, Hirano T. The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors. Cancer Sci 2003; 94: 1029-33.
159. Yamasaki S, Nishida K, Yoshida Y, Itoh M, Hibi M, Hirano T. Gab1 is required for EGF receptor signaling and the transformation by activated ErbB2. Oncogene 2003; 22: 1546-56.
160. Gillgrass A, Cardiff RD, Sharan N, Kannan S, Muller WJ. Epidermal growth factor receptor-dependent activation of Gab1 is involved in ErbB-2-mediated mammary tumor progression. Oncogene 2003; 22: 9151-5.
161. Jackson JG, St Clair P, Sliwkowski MX, Brattain MG. Blockade of epidermal growth factor- or heregulin-dependent ErbB2 activation with the anti-ErbB2 monoclonal antibody 2C4 has divergent downstream signaling and growth effects. Cancer Res 2004, 64: 2601-9.
162. Daly RJ, Gu H, Parmar J, Malaney S, Lyons RJ, Kairouz R, et al. The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer. Oncogene 2002; 21: 5175-81.
163. Sattler M, Mohi MG, Pride YB, Quinnan LR, Maloof NA, Podar K, et al. Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell 2002; 1: 479-92.
164. Yart A, Mayeux. P, Raynal P. Gabl, SHP-2 and other novel regulators of Ras: targets for anticancer drug discovery? Curr Cancer Drug Targets 2003; 3: 177-92.
165. Gelkop S, Babichev Y, Kalifa R, Tamir A, Isakov N. Involvement of crk adapter proteins in regulation of lymphoid cell functions. Immunol. Res 2003; 28: 79-91.
166. Matsuda M, Hashimoto Y, Muroya K, Hasegawa H, Kurata T, Tanaka S, et al. CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factor-induced activation of Ras in PC12 cells. Mol Cell Biol 1994; 14: 5495-500.
167. Knudsen BS, Feller SM, Hanafusa. H. Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk. J Biol Chem 1994; 269: 32781-7.
168. Gotoh T, Hattori S, Nakamura S, Kitayama H, Noda M, Takai Y, et al. Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G. Mol Cell Biol 1995; 15: 6746-53.
169. van den Berghe N, Cool RH, Horn G, Wittinghofer A. Biochemical characterization of C3G: an exchange factor that discriminates between Rap1 and Rap2 and is not inhibited by Rap1A(S17N). Oncogene 1997; 15: 845-50.
170. Ohba Y, Mochizuki N, Matsuo K, Yamashita S, Nakaya M, Hashimoto Y, et al. Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade. Mol Cell Biol 2000; 20: 6074-83.
171. Hirata T, Nagai H, Koizumi K, Okino K, Harada A, Onda M, et al. Amplification, up-regulation and over-expression of C3G (CRK SH3 domain-binding guanine nucleotide-releasing factor) in non-small cell lung cancers. J Hum Genet 2004; 49: 290-5.
172. Stork PJ. Does Rap1 deserve a bad Rap? Trends Biochem Sci 2003; 28: 267-75.
173. Bos JL, de Rooij J, Reedquist KA. Rap1 signalling: adhering to new models. Nat Rev Mol Cell Biol 2001; 2: 369-77.
174. Hattori M, Minato N. Rap1 GTPase: functions, regulation, and malignancy. J Biochem (Tokyo) 2003; 134: 479-84.
175. Altschuler DL, Ribeiro-Neto F. Mitogenic and oncogenic properties of the small G protein Rap1b. Proc Natl Acad Sci USA 1998; 95: 7475-9.
176. Kitayama H, Sugimoto Y, Matsuzaki T, Ikawa Y, Noda M. A rasrelated gene with transformation suppressor activity. Cell 1989; 56: 77-84.
177. Largaespada. DA. A bad rap: Rap1 signaling and oncogenesis. Cancer Cell 2003; 4: 3-4.
178. Ishida D, Kometani K, Yang H, Kakugawa K, Masuda K, Iwai K, et al. Myeloproliferative stem cell disorders by deregulated Rap1 activation in SPA-1-deficient mice. Cancer Cell 2003; 4: 55-65.
179. Vossler MR, Yao H, York RD, Pan MG, Rim CS, Stork PJ. cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway. Cell 1997; 89: 73-82.
180. York RD, Yao H, Dillon T, Ellig CL, Eckert SP, McCleskey EW, et al. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 1998; 392: 622-6.
181. Boettner B, Govek EE, Cross J, Van Aelst L. The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin. Proc Natl Acad Sci USA 2000; 97: 9064-9.
182. Kao S, Jaiswal RK, Kolch W, Landreth GE. Identification of the mechanisms regulating the differential activation of the mapk cascade by epidermal growth factor and nerve growth factor in PC12 cells. J Biol Chem 2001; 276: 18169-77.
183. Su L, Hattori M, Moriyama M, Murata N, Harazaki M, Kaibuchi K, et al. AF-6 controls integrin-mediated cell adhesion by regulating Rap1 activation through the specific recruitment of Rap1GTP and SPA-1. J Biol Chem 2003; 278: 15232-8.
184. Arevalo JC, Yano H, Teng KK, Chao MV. A unique pathway for sustained neurotrophin signaling through an ankyrin-rich membrane-spanning protein. EMBO J 2004; 23: 2358-68.
185. Katagiri K, Maeda A, Shimonaka M, Kinashi T. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol 2003; 4: 741-8.
186. Tanaka S, Hanafusa H. Guanine-nucleotide exchange protein C3G activates JNK1 by a ras-independent mechanism. JNK1 activation inhibited by kinase negative forms of MLK3 and DLK mixed lineage kinases. J Biol Chem 1998; 273: 1281-4.
187. Zhu T, Goh EL, LeRoith D, Lobie PE. Growth hormone stimulate the formation of a multiprotein signaling complex involving p130(Cas) and CrkII. Resultant activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). J Biol Chem 1998; 273: 33864-75.
188. Machida N, Umikawa M, Takei K, Sakima N, Myagmar BE, Taira K, et al. Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase. 4 Biol Chem 2004; 279: 15711-4.
189. Smith JM, Mayer BJ. Abl: mechanisms of regulation and activation. Front Biosci 2002; 7: d31-42.
190. Pendergast AM. The Ab1 family kinases: mechanisms of regulation and signaling. Adv Cancer Res 2002; 85: 51-100.
191. Woodring PJ, Hunter T, Wang JY. Regulation of F-actindependent processes by the Ab1 family of tyrosine kinases. J Cell Sci 2003; 116: 2613-26.
192. Van Etten RA. c-Ab1 regulation: a tail of two lipids. Curr Biol 2003; 13: R608-10.
193. Wang JY. Controlling Ab1: auto-inhibition and co-inhibition? Nat Cell Biol 2004; 6: 3-7.
194. Hantschel O, Superti-Furga G. Regulation of the c-Ab1 and Bcr-Ab1 tyrosine kinases. Nat Rev Mol Cell Biol 2004; 5: 33-44.
195. Sini P, Cannas A, Koleske AJ, Di Fiore PP, Scita G. Ab1-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation. Nat Cell Biol 2004; 6: 268-74.
196. Fukui Y, Kornbluth S, Jong SM, Wang LH, Hanafusa H. Phosphatidylinositol kinase type I activity associates with various oncogene products. Oncogene Res 1989; 4: 283-92.
197. Sattler M, Salgia R, Okuda K, Uemura N, Durstin MA, Pisick E, et al. The proto-oncogene product p120CBL and the adaptor proteins CRKL and c-CRK link c-ABL, p190BCR/ABL and p210BCR/ABL to the phosphatidylinositol-3′ kinase pathway. Oncogene 1996; 12: 839-46.
198. Husson H, Mograbi B, Schmid-Antomarchi H, Fischer S, Rossi B. CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cb1, PI 3-kinase, Crk-II and Grb2. Oncogene 1997; 14: 2331-8.
199. Li E, Stupack DG, Brown SL, Klemke R, Schlaepfer DD, Nemerow GR. Association of p130CAS with phosphatidylinositol-3-OH kinase mediates adenovirus cell entry. J Biol Chem 2000; 275: 14729-35.
200. Goh EL, Zhu T, Yakar S, LeRoith D, Lobie PE. CrkII participation in the cellular effects of growth hormone and insulin-like growth factor-1. Phosphatidylinositol-3 kinase dependent and independent effects. J Biol Chem 2000; 275: 17683-92.
201. Akagi T, Shishido T, Murata K, Hanafusa H. v-Crk activates the phosphoinositide 3-kinase/AKT pathway in transformation. Proc Natl Acad Sci USA 2000; 97: 7290-5.
202. Riggins RB, DeBerry RM, Toosarvandani MD, Bouton AH. Src-dependent association of Cas and p85 phosphatidylinositol 3′-kinase in v-crk-transformed cells. Mol Cancer Res 2003; 1: 428-37.
203. Ward SG, Finan P. Isoform-specific phosphoinositide 3-kinase inhibitors as therapeutic agents. Curr Opin Pharmacol 2003; 3: 426-34.
204. Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 2003; 4: 257-62.
205. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004; 304: 554.
206. Cote JF, Vuori K. Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. J Cell Sci 2002; 115: 4901-13.
207. Nishihara H, Maeda M, Oda A, Tsuda M, Sawa H, Nagashima K, et al. DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines. Blood 2002; 100: 3968-74.
208. Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer 2002; 2: 133-42.
209. Lozano E, Betson M, Braga VM. Tumor progression: Small GTPases and loss of cell-cell adhesion. Bioessays 2003; 25: 452-63.
210. Steeg PS. Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer 2003; 3: 55-63.
211. Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, et al. Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol 2002; 4: 574-82.
212. Erickson JW, Cerione RA. Structural elements, mechanism, and evolutionary convergence of Rho protein-guanine nucleotide exchange factor complexes. Biochemistry 2004; 43: 837-42.
213. Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M. Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Genes Dev 1998; 12: 3331-6.
214. Albert ML, Kim JI, Birge RB. alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells. Nat Cell Biol 2000; 2: 899-905.
215. Fukui Y, Hashimoto O, Sanui T, Oono T, Koga H, Abe M, et al. Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature 2001; 412: 826-31.
216. Reif K, Cyster J. The CDM protein DOCK2 in lymphocyte migration. Trends Cell Biol 2002; 12: 368-73.
217. Sanui T, Inayoshi A, Noda M, Iwata E, Stein JV, Sasazuki T, et al. DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1. Blood 2003; 102: 2948-50.
218. Sanui T, Inayoshi A, Noda M, Iwata E, Oike M, Sasazuki T, et al. DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, in T cells. Immunity 2003; 19: 119-29.
219. Janardhan A, Swigut T, Hill B, Myers MP, Skowronski J. HIV-1 Nef Binds the DOCK2-ELMO1 Complex to Activate Rac and Inhibit Lymphocyte Chemotaxis. PLoS Biol 2004; 2: E6.
220. Kashiwa A, Yoshida H, Lee S, Paladino T, Liu Y, Chen Q, et al. Isolation and characterization of novel presenilin binding protein. J Neurochem 2000; 75: 109-16.
221. Chen Q, Kimura H, Schubert D. A novel mechanism for the regulation of amyloid precursor protein metabolism. J Cell Biol 2002; 158: 79-89.
222. de Silva MG, Elliott K, Dahl HH, Fitzpatrick E, Wilcox S, Delatycki M, et al. Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is associated with an attention deficit hyperactivity disorder-like phenotype. J Med Genet 2003; 40: 733-40.
223. Namekata K, Enokido Y, Iwasawa K, Kimura H. MOCA induces membrane spreading by activating Racl. J Biol Chem 2004; 279: 14331-7.
224. Yajnik V, Paulding C, Sordella R, McClatchey AI, Saito M, Wahrer DC, et al. DOCK4, a GTPase activator, is disrupted during tumorigenesis. Cell 2003; 112: 673-84.
225. Felschow DM, McVeigh ML, Hoehn GT, Civin Cl, Fackler MJ. The adapter protein CrkL associates with CD34. Blood 2001; 97: 3768-75.
226. Smith JJ, Richardson DA, Kopf J, Yoshida M, Hollingsworth RE, Kornbluth S. Apoptotic regulation by the Crk adapter protein mediated by interactions with Wee1 and Crm1/exportin. Mol Cell Biol 2002; 22: 1412-23.
227. Clark SG, Stern MJ, Horvitz HR. C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains. Nature 1992; 356: 340-4.
228. Downward J. The GRB2/Sem-5 adaptor protein. FEBS Lett 1994; 338: 113-7.
229. Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, et al. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 1992; 70: 431-42.
230. Rozakis-Adcock M, McGlade J, Mbamalu G, Pelicci G, Daly R, Li W, et al. Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases. Nature 1992; 360: 689-92.
231. Olivier JP, Raabe T, Henkemeyer M, Dickson B, Mbamalu G, Margolis B, et al. A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Cell 1993; 73: 179-91.
232. Skolnik EY, Lee CH, Batzer A, Vicentini LM, Zhou M, Daly R, et al. The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. EMBO J 1993; 12: 1929-36.
233. Gale NW, Kaplan S, Lowenstein EJ, Schlessinger J, Bar-Sagi D. Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras. Nature 1993; 363: 88-92.
234. Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM, Weinberg RA. Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Nature 1993; 363: 45-51.
235. Rozakis-Adcock M, Fernley R, Wade J, Pawson T, Bowtell D. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1. Nature 1993; 363: 83-5.
236. Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, et al. Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Nature 1993; 363: 85-8.
237. Buday L, Downward J. Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell 1993; 73: 611-20.
238. Chardin P, Camonis JH, Gale NW, van Aelst L, Schlessinger J, Wigler MH, et al. Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science 1993; 260: 1338-43.
239. Skolnik EY, Batzer A, Li N, Lee CH, Lowenstein E, Mohammadi M, et al. The function of GRB2 in linking the insulin receptor to Ras signaling pathways. Science 1993; 260: 1953-5.
240. Bar-Sagi D, Rotin D, Batzer A, Mandiyan V, Schlessinger J. SH3 domains direct cellular localization of signaling molecules. Cell 1993; 74: 83-91.
241. Koretzky GA. The role of Grb2-associated proteins in T-cell activation. Immunol Today 1997; 18: 401-6.
242. Takenawa T, Miki H, Matuoka K. Signaling through Grb2/Ash-control of the Ras pathway and cytoskeleton. Curr Top Microbiol Immunol 1998; 228: 325-42.
243. Tari AM, Lopez-Berestein G. GRB2: a pivotal protein in signal transduction. Semin Oncol 2001; 28: 142-7.
244. Wasylyk B, Hagman J, Gutierrez-Hartmann A. Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway. Trends Biochem Sci 1998; 23: 213-6.
245. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001; 22: 153-83.
246. Hazzalin CA, Mahadevan LC. MAPK-regulated transcription: a continuously variable gene switch? Nat Rev Mol Cell Biol 2002; 3: 30-40.
247. Murphy LO, Smith S, Chen RH, Fingar DC, Blenis J. Molecular interpretation of ERK signal duration by immediate early gene products. Nat Cell Biol 2002; 4: 556-64.
248. Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, et al. Signal transduction mediated by the Ras/Raf(MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 2003; 17: 1263-93.
249. Cheng AM, Saxton TM, Sakai R, Kulkarni S, Mbamalu G, Vogel W, et al. Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation. Cell 1998; 95: 793-803.
250. Saxton TM, Cheng AM, Ong SH, Lu Y, Sakai R, Cross JC, et al. Gene dosage-dependent functions for phosphotyrosine-Grb2 signaling during mammalian tissue morphogenesis. Curr Biol 2001; 11: 662-70.
251. Gong Q, Cheng AM, Akk AM, Alberola-Ila J, Gong G, Pawson T, et al. Disruption of T cell signaling networks and development by Grb2 haploid insufficiency. Nat Immunol 2001; 2: 29-36.
252. Zhang S, Ren J, Khan MF, Cheng AM, Abendschein D, Muslin AJ. Grb2 is required for the development of neointima in response to vascular injury. Arterioscler Thromb Vasc Biol 2003; 23: 1788-93.
253. Rauh MJ, Blackmore V, Andrechek ER, Tortorice CG, Daly R, Lai VK, et al. Accelerated mammary tumor development in mutant polyomavirus middle T transgenic mice expressing elevated levels of either the Shc or Grb2 adapter protein. Mol Cell Biol 1999; 19: 8169-79.
254. Daly RJ, Binder MD, Sutherland RL. Overexpression of the Grb2 gene in human breast cancer cell lines. Oncogene 1994; 9: 2723-7.
255. Verbeek BS, Adriaansen-Slot SS, Rijksen G, Vroom TM. Grb2 overexpression in nuclei and cytoplasm of human breast cells: a histochemical and biochemical study of normal and neoplastic mammary tissue specimens. J Pathol 1997; 183: 195-203.
256. Salcini AE, McGlade J, Pelicci G, Nicoletti I, Pawson T, Pelicci PG. Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of She proteins. Oncogene 1994; 9: 2827-36.
257. Tanaka S, Ito T, Wands JR. Neoplastic transformation induced by insulin receptor substrate-1 overexpression requires an interaction with both Grb2 and Syp signaling molecules. J Biol Chem 1996; 271: 14610-6.
258. Ravichandran KS. Signaling via Shc family adapter proteins. Oncogene 2001; 20: 6322-30.
259. Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, et al. A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell 1997; 89: 693-702.
260. Ong SH, Hadari YR, Gotoh N, Guy GR, Schlessinger J, Lax I. Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins. Proc Natl Acad Sci USA 2001; 98: 6074-9.
261. Wong A, Lamothe B, Lee A, Schlessinger J, Lax I, Li A. FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl. Proc Natl Acad Sci USA 2002; 99: 6684-9.
262. Cantrell D. The real LAT steps forward. Trends Cell Biol 1998; 8: 180-2.
263. Wange RL. LAT, the linker for activation of T cells: a bridge between T cell-specific and general signaling pathways. Sci STKE 2000; 2000: RE1.
264. Wonerow P, Watson SP. The transmembrane adapter LAT plays a central role in immune receptor signalling. Oncogene 2001; 20: 6273-83.
265. Sommers CL, Samelson LE, Love PE. LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways. Bioessays 2004; 26: 61-7.
266. Dikic I, Giordano S. Negative receptor signalling. Curr Opin Cell Biol 2003; 15: 128-35.
267. Thien CB, Langdon WY. Cbl: many adaptations to regulate protein tyrosine kinases. Nat Rev Mol Cell Biol 2001; 2: 294-307.
268. Sanjay A, Horne WC, Baron R. The Cbl family: ubiquitin ligases regulating signaling by tyrosine kinases. Sci STKE 2001; 2001: PE40.
269. Peschard P, Park M. Escape from Cbl-mediated downregulation: a recurrent theme for oncogenic deregulation of receptor tyrosine kinases. Cancer Cell 2003; 3: 519-23.
270. Hanafusa H, Torii S, Yasunaga T, Nishida E. Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway. Nat Cell Biol 2002; 4: 850-8.
271. Hanafusa H, Torii S, Yasunaga T, Matsumoto K, Nishida E. Shp2, an SH2-containing Protein-tyrosine Phosphatase, Positively Regulates Receptor Tyrosine Kinase Signaling by Dephosphorylating and Inactivating the Inhibitor Sprouty. J Biol Chem 2004; 279: 22992-22995.
272. Neel BG, Gu H, Pao L. The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci 2003; 28: 284-93.
273. Zhang SQ, Yang W, Kontaridis MI, Bivona TG, Wen G, Araki T, et al. Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Mol Cell 2004; 13: 341-55.
274. Rhee SG, Bae YS, Lee SR, Kwon J. Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE 2000; 2000: PE1.
275. Meng TC, Fukada T, Tonks NK. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell 2002; 9: 387-99.
276. Hall BE, Yang SS, Bar-Sagi D. Autoinhibition of Sos by intramolecular interactions. Front Biosci 2002; 7: d288-94.
277. Nimnual A, Bar-Sagi D. The two hats of SOS. Sci STKE 2002; 2002: PE36.
278. Nielsen KH, Papageorge AG, Vass WC, Willumsen BM, Lowy DR. The Ras-specific exchange factors mouse Sos1 (mSos 1) and mSos2 are regulated differently: mSos2 contains ubiquitination signals absent in mSos1. Mol Cell Biol 1997; 17: 7132-8.
279. Qian X, Esteban L, Vass WC, Upadhyaya C, Papageorge AG, Yienger K, et al. The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties. EMBO J 2000; 19: 642-54.
280. Yang SS, Van Aelst L, Bar-Sagi D. Differential interactions of human Sos1 and Sos2 with Grb2. J Biol Chem 1995; 270: 18212-5.
281. Marshall CJ. The ras oncogenes. J Cell Sci Suppl 1988; 10: 157-69.
282. Bos JL. ras oncogenes in human cancer: a review. Cancer Res 1989; 49: 4682-9.
283. Feller SM, Tuchscherer G, Voss J. High affinity molecules disrupting GRB2 protein complexes as a therapeutic strategy for chronic myelogenous leukaemia. Leuk Lymphoma 2003; 44: 411-27.
284. Ferguson MR, Fan X, Mukherjee M, Luo J, Khan R, Ferreon JC, et al. Directed discovery of bivalent peptide ligands to an SH3 domain. Protein Sci 2004; 13: 626-32.
285. Vidal M, Liu WQ, Lenoir C, Salzmann J, Gresh N, Garbay C. Design of peptoid analogue dimers and measure of their affinity for Grb2 SH3 domains. Biochemistry 2004; 43: 7336-44.
286. Gay B, Suarez S, Caravatti G, Furet P, Meyer T, Schoepfer J. Selective GRB2 SH2 inhibitors as anti-Ras therapy. Int J Cancer 1999; 83: 235-41.
287. Vu CB. Recent advances in the design and synthesis of SH2 inhibitors of Src, Grb2 and ZAP-70. Curr Med Chem 2000; 7: 1081-100.
288. Lung FD, Tsai JY. Grb2 SH2 domain-binding peptide analogs as potential anticancer agents. Biopolymers 2003; 71: 132-40.
289. Liu WQ, Vidal M, Olszowy C, Million E, Lenoir C, Dhotel H, et al. Structure-activity relationships of small phosphopeptides, inhibitors of Grb2 SH2 domain, and their prodrugs. J Med Chem 2004; 47: 1223-33.
290. Innocenti M, Tenca P, Frittoli E, Faretta M, Tocchetti A, Di Fiore PP, et al. Mechanisms through which Sos-1 coordinates the activation of Ras and Rac. J Cell Biol 2002; 156: 125-36.
291. Fan PD, Goff SP. Abl interactor l binds to sos and inhibits epidermal growth factor- and v-Abl-induced activation of extracellular signal-regulated kinases. Mol Cell Biol 2000; 20: 7591-601.
292. Hibi M, Hirano T. Gab-family adapter molecules in signal transduction of cytokine and growth factor receptors, and T and B cell antigen receptors. Leuk Lymphoma 2000; 37: 299-307.
293. Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ. A Grb2-associated docking protein in EGF- and insulin-receptor signalling. Nature 1996; 379: 560-4.
294. Gu H, Pratt JC, Burakoff SJ, Neel BG. Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation. Mol Cell 1998; 2: 729-40.
295. Lock LS, Royal I, Naujokas MA, Park M. Identification of an atypical Grb2 carboxyl-terminal SH3 domain binding site in Gab docking proteins reveals Grb2-dependent and -independent recruitment of Gabl to receptor tyrosine kinases. J Biol Chem 2000; 275: 31536-45.
296. Schaeper U, Gehring NH, Fuchs KP, Sachs M, Kempkes B, Birchmeier W. Coupling of Gabl to c-Met, Grb2, and Shp2 mediates biological responses. J Cell Biol 2000; 149: 1419-32.
297. Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, et al. The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gabl and SLP-76 which lack the SH3-typical P-x-x-P core motif. Oncogene 2001; 20: 1052-62.
298. Bourgin C, Bourette RP, Arnaud S, Liu Y, Rohrschneider LR, Mouchiroud G. Induced expression and association of the Mona/Gads adapter and Gab3 scaffolding protein during monocyte/macrophage differentiation. Mol Cell Biol 2002; 22: 3744-56.
299. Sugiyama Y, Tomoda K, Tanaka T, Arata Y, Yoneda-Kato N, Kato J. Direct binding of the signal-transducing adaptor Grb2 facilitates down-regulation of the cyclin-dependent kinase inhibitor p27Kipl. J Biol Chem 2001; 276: 12084-90.
300. Moeller SJ, Head ED, Sheaff RJ. p27Kipl inhibition of GRB2-SOS formation can regulate Ras activation. Mol Cell Biol 2003; 23: 3735-52.
301. Blain SW, Scher HI, Cordon-Cardo C, Koff A. p27 as a target for cancer therapeutics. Cancer Cell 2003; 3: 111-5.
302. Besson A, Gurian-West M, Schmidt A, Hall A, Roberts JM. p27Kipl modulates cell migration through the regulation of RhoA activation. Genes Dev 2004; 18: 862-76.
303. Collard JG. Cancer: Kip moving. Nature 2004; 428: 705-8.
304. Borinstein SC, Hyatt MA, Sykes VW, Straub RE, Lipkowitz S, Boulter J, et al. SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins. Cell Signal 2000; 12: 769-79.
305. Tu Z, Ninos JM, Ma Z, Wang JW, Lemos MP, Desponts C, et al. Embryonic and hematopoietic stem cells express a novel SH2- containing inositol 5′-phosphatase isoform that partners with the Grb2 adapter protein. Blood 2001; 98: 2028-38.
306. Wheeler M, Domin J. Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2. Mol Cell Biol 2001; 21: 6660-7.
307. Zhou D, Chen B, Ye JJ, Chen S. A novel crosstalk mechanism between nuclear receptor-mediated and growth factor/Ras-mediated pathways through PNRC-Grb2 interaction. Oncogene 2004; 23: 5394-404.
308. Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, et al. Cloning of a Grb2 isoform with apoptotic properties. Science 1994; 264: 971-4.
309. Li X, Multon MC, Henin Y, Schweighoffer F, Venot C, Josef J, et al. Grb3-3 is up-regulated in HIV-1-infected T-cells and can potentiate cell activation through NFATc. J Biol Chem 2000; 275: 30925-33.
310. Li X, Multon MC, Henin Y, Schweighoffer F, Venot C, La Vecchio J, et al. Upregulation of the apoptosis-associated protein Grb3-3 in HIV- 1 -infected human CD4(+) lymphocytes. Biochem Biophys Res Commun 2000; 276: 362-70.
311. Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz; R, Ni J. Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway. J Biol Chem 1996; 271: 12129-32.
312. Shen R, Ouyang YB, Qu CK, Alonso A, Sperzel L, Mustelin T, et al. Grap negatively regulates T-cell receptor-elicited lymphocyte proliferation and interleukin-2 induction. Mol Cell Biol 2002; 22: 3230-6.
313. Shiraiwa H, Takei M, Yoshikawa T, Azuma T, Kato M, Mitamura K, et al. Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary glands of MRL/lpr mice and patients with Sjogren's syndrome. J Int Med Res 2004; 32: 284-91.
314. Bourette RP, Arnaud S, Myles GM, Blanchet JP, Rohrschneider LR, Mouchiroud G. Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development. EMBO J 1998; 17: 7273-81.
315. Liu SK, McGlade CJ. Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc. Oncogene 1998; 17: 3073-82.
316. Qiu M, Hua S, Agrawal M, Li G, Cai J, Chan E, et al. Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab- 1. Biochem Biophys Res Commun 1998; 253: 443-7.
317. Law CL, Ewings MK, Chaudhary PM, Solow SA, Yun TJ, Marshall AJ, et al. GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation. J Exp Med 1999; 189: 1243-53.
318. Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, et al. Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT. J Exp Med 1999; 189: 1383-90.
319. Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA. GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28. J Immunol 2000; 164: 5805-14.
320. Liu SK, Berry DM, McGlade CJ. The role of Gads in hematopoietic cell signalling. Oncogene 2001; 20: 6284-90.
321. Burack WR, Cheng AM, Shaw AS. Scaffolds, adaptors and linkers of TCR signaling: theory and practice. Curr Opin Immunol 2002; 14:312-6.
322. Geng L, Rudd CE. Signalling scaffolds and adaptors in T-cell immunity. Br J Haematol 2002; 116: 19-27.
323. Yoder J, Pham C, Iizuka YM, Kanagawa O, Liu SK, McGlade J, et al. Requirement for the SLP-76 adaptor GADS in T cell development. Science 2001; 291: 1987-91.
324. Clements JL, Yang B, Ross-Barta SE, Eliason SL, Hrstka RF, Williamson RA, et al. Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development. Science 1998; 281: 416-9.
325. Pivniouk V, Tsitsikov E, Swinton P, Rathbun G, Alt FW, Geha RS. Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76. Cell 1998; 94: 229-38.
326. Liu SK, Smith CA, Arnold R, Kiefer F, McGlade CJ. The adaptor protein Gads (Grb2-related adaptor downstream of Shc) is implicated in coupling hemopoietic progenitor kinase-1 to the activated TCR. J Immunol 2000; 165: 1417-26.
327. Liu SK, Fang N, Koretzky GA, McGlade CJ. The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. Curr Biol 1999; 9: 67-75.
328. Rudd CE, Wang H. Hematopoietic adaptors in T-cell signaling: potential applications to transplantation. Am J Transplant 2003; 3: 1204-10.
329. Singer AL, Bunnell SC, Obstfeld AE, Jordan MS, Wu JN, Myung PS, et al. Roles of the proline-rich domain in SLP-76 subcellular localization and T cell function. J Biol Chem 2004; 279: 15481-90.
330. Kaneko T, Kumasaka T, Ganbe T, Sato T, Miyazawa K, Kitamura N, et al. Structural insight into modest binding of a non-PXXP ligand to the signal transducing adaptor molecule-2 Src homology 3 domain. J Biol Chem 2003; 278: 48162-8.
331. Braverman LE, Quilliam LA. Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. J Biol Chem 1999; 274: 5542-9.
332. Coutinho S, Jahn T, Lewitzky M, Feller S, Hutzler P, Peschel C, et al. Characterization of Grb4, an adapter protein interacting with Bcr-Abl. Blood 2000; 96: 618-24.
333. Cowan CA, Henkemeyer M. The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals. Nature 2001; 413: 174-9.
334. Li W, Fan J, Woodley DT. Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton. Oncogene 2001; 20: 6403-17.
335. Buday L, Wunderlich L, Tamas P. The Nck family of adapter proteins: regulators of actin cytoskeleton. Cell Signal 2002; 14: 723-31.
336. Chou MM, Fajardo JE, Hanafusa H. The SH2- and SH3-containing Nck protein transforms mammalian fibroblasts in the absence of elevated phosphotyrosine levels. Mol Cell Biol 1992; 12: 5834-42.
337. Feller SM, Knudsen B, Hanafusa H. Cellular proteins binding to the first Src homology 3 (SH3) domain of the proto-oncogene product c-Crk indicate Crk-specific signaling pathways. Oncogene 1995; 10: 1465-73.
338. Hu Q, Milfay D, Williams LT. Binding of NCK to SOS and activation of ras-dependent gene expression. Mol Cell Biol 1995; 15: 1169-74.
339. Stoletov KV, Gong C, Terman BI. Nck and Crk mediate distinct VEGF-induced signaling pathways that serve overlapping functions in focal adhesion turnover and integrin activation. Exp Cell Res 2004; 295: 258-68.
340. Nottage M, Siu LL. Rationale for Ras and raf-kinase as a target for cancer therapeutics. Curr Pharm Des 2002; 8: 2231-42.
341. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003; 3: 11-22.
342. Lorimer IA. Mutant epidermal growth factor receptors as targets for cancer therapy. Curr Cancer Drug Targets 2002; 2: 91-102.
343. Hirsch FR, Scagliotti GV, Langer CJ, Varella-Garcia M, Franklin WA. Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. Lung Cancer 2003; 41 (Suppl 1): S29-42.
344. Menard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene 2003; 22: 6570-8.
345. Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer 2004; 4: 361-70.
346. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-82.
347. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707-12.
348. Saucier C, Khoury H, Lai KM, Peschard P, Dankort D, Nanjokas MA, et al. The Shc adaptor protein is critical for VEGF induction by Met/HGF and ErbB2 receptors and for early onset of tumor angiogenesis. Proc Natl Acad Sci USA 2004; 101: 2345-50.
349. Cohen MH, Williams GA, Sridhara R, Chen G, McGuinn WD, Jr., Morse D, et al. United States Food and Drug Administration Drug Approval summary: Gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 2004; 10: 1212-8.
350. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497-500.
351. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350: 2129-39.
352. Dancey JE. Agents targeting ras signaling pathway. Curr Pharm Des 2002; 8: 2259-67.
353. Lancet JE, Karp JE. Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy. Blood 2003; 102: 3880-9.
354. Zhu K, Hamilton AD, Sebti SM. Farnesyltransferase inhibitors as anticancer agents: current status. Curr Opin Investig Drugs 2003; 4: 1428-35.
355. Mazieres J, Pradines A, Favre G. Perspectives on farnesyl transferase inhibitors in cancer therapy. Cancer Left 2004; 206: 159-67.
356. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949-54.
357. Tuveson DA, Weber BL, Herlyn M. BRAF as a potential therapeutic target in melanoma and other malignancies. Cancer Cell 2003; 4: 95-8.
358. Mercer KE, Pritchard CA. Raf proteins and cancer: B-Raf is identified as a mutational target. Biochim Biophys Acta 2003; 1653: 25-40.
359. Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004; 116: 855-67.
360. Wilhelm S, Chien DS. BAY 43-9006: preclinical data. Curr Pharm Des 2002; 8: 2255-7.
361. Hotte SJ, Hirte HW. BAY 43-9006: early clinical data in patients with advanced solid malignancies. Curr Pharm Des 2002; 8: 2249-53.
362. Lee JT, McCubrey JA. BAY-43-9006 Bayer/Onyx. Curr Opin Investig Drugs 2003; 4: 757-63.
363. Bollag G, Freeman S, Lyons JF, Post LE. Raf pathway inhibitors in oncology. Curr Opin Investig Drugs 2003; 4: 1436-41.
364. Allen LF, Sebolt-Leopold J, Meyer MB. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol 2003; 30: 105-16.
365. Sebolt-Leopold JS. MEK Inhibitors: a therapeutic approach to targeting the Ras-MAP kinase pathway in tumors. Curr Pharm Des 2004; 10: 1907-14.
366. Madhusudan S, Ganesan TS. Tyrosine kinase inhibitors in cancer therapy. Clin Biochem 2004; 37: 618-35.
367. Lane DP, Fischer PM. Turning the key on p53. Nature 2004; 427: 789-90.
368. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303: 844-8.
369. Chene P. Inhibition of the p53-MDM2 interaction: targeting a protein-protein interface. Mol Cancer Res 2004; 2: 20-8.
370. Fischer PM, Lane DP. Small-molecule inhibitors of the p53 suppressor HDM2: have protein-protein interactions come of age as drug targets? Trends Pharmacol Sci 2004; 25: 343-6.
371. Momand J, Jung D, Wilczynski S, Niland J. The MDM2 gene amplification database. Nucleic Acids Res 1998; 26: 3453-9.
372. Schimmer AD, Welsh K, Pinilla C, Wang Z, Krajewska M, Bonneau MJ, et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 2004; 5: 25-35.
373. Huang Y, Lu M, Wu H. Antagonizing XIAP-mediated caspase-3 inhibition. Achilles' heel of cancers? Cancer Cell 2004; 5: 1-2.
374. Toogood PL. Inhibition of protein-protein association by small molecules: approaches and progress. J Med Chem 2002; 45: 1543-58.
375. Gadek TR, Nicholas JB. Small molecule antagonists of proteins. Biochem
376. Brugge JS. New intracellular targets for therapeutic drug design. Science 1993; 260: 918-9.
377. Smithgall TE. SH2 and SH3 domains: potential targets for anticancer drug design. J Pharmacol Toxicol Methods 1995; 34: 125-32.
378. Dalgarno DC, Botfield MC, Rickles RJ. SH3 domains and drug design: ligands, structure, and biological function. Biopolymers 1997; 43: 383-400.
379. Arteaga CL, Baselga J. Tyrosine kinase inhibitors: why does the current process of clinical development not apply to them? Cancer Cell 2004; 5: 525-31.
380. Boulay A, Zumstein-Mecker S, Stephan C, Beuvink I, Zilbermann F, Haller R, et al. Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res 2004; 64: 252-61.
381. Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 1998; 279: 377-80.
382. Kolonin M, Pasqualini R, Arap W. Molecular addresses in blood vessels as targets for therapy. Curr Opin Chem Biol 2001; 5: 308-13.
383. Ruoslahti E. Specialization of tumour vasculature. Nat Rev Cancer 2002; 2: 83-90.
384. Nicholls A, Sharp KA, Honig B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 1991; 11: 281-96.
385. Fackelmayer FO. Nuclear architecture and gene expression in the quest for novel therapeutics. Curr Pharm Design 2004; 10(23): 2851-60.
386. Luskova P, Draber P. Modulation of the Fcepsilon receptor I signaling by tyrosine kinase inhibitors: search for therapeutic targets of inflammatory and allergy diseases. Curr Pharm Design 2004; 10(15): 1727-37.
387. Sakoff JA, McCluskey A. Protein phosphatase inhibition: structure based design. Towards new therapeutic agents. Curr Pharm Design 2004; 10(10): 1139-59.