Molecular basis for Rho GTPase signaling specificity

Breast Cancer Research and Treatment

Volumn 84, Issue 1, 2004, Pages 61-71

  Karnoub, Antoine E ^a   Symons, Marc ^b   Campbell, Sharon L ^a   Der, Channing J ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b Northwell Health   (United States)

Author keywords

Db1; DH domain; Effector; GTPase; Oncogene; Rho; Signaling; Specificity; Transformation

Indexed keywords

PROTEIN CDC42; RAC1 PROTEIN; RAS PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHO KINASE;

BINDING SITE; BREAST CANCER; CRYSTAL STRUCTURE; ENZYME ACTIVATION; ENZYME BINDING; ENZYME SPECIFICITY; EXTRACELLULAR SPACE; GENE ACTIVITY; GENE SEQUENCE; HUMAN; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

BREAST NEOPLASMS; ENZYME ACTIVATION; FEMALE; GTPASE-ACTIVATING PROTEINS; GUANINE NUCLEOTIDE DISSOCIATION INHIBITORS; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HUMANS; MUTATION; RHO GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION;

EID: 1642393863     PISSN: 01676806     EISSN: None     Source Type: Journal    
DOI: 10.1023/B:BREA.0000018427.84929.5c     Document Type: Review

References (104)

1. Downward J: Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3: 11-22, 2003
2. Cox AD, Der CJ: Ras family signaling: therapeutic targeting. Cancer Biol Ther 1: 599-606, 2002
3. Sahai E, Marshall CJ: RHO-GTPases and cancer. Nat Rev Cancer 2: 133-142, 2002
4. Boettner B, Van Aelst L: The role of Rho GTPases in disease development. Gene 286: 155-174, 2002
5. Karnoub AE, Der CJ: Rho family GTPases and cellular transformation. In: Marc Symons (ed) Signal Transduction: RhoGTPases. Landes Biosciences Pub. Co., pp 165-186, 2003
6. Fritz G, Just I, Kaina B: Rho GTPases are over-expressed in human tumors. Int J Cancer 81: 682-687, 1999
7. Fritz G, Brachetti C, Bahlmann F, Schmidt M, Kaina B: Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. Br J Cancer 87: 635-644, 2002
8. van Golen KL, Davies S, Wu ZF, Wang Y, Bucana CD, Root H, Chandrasekharappa S, Strawderman M, Ethier SP, Merajver SD: A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype. Clin Cancer Res 5: 2511-2519, 1999
9. van Golen KL, Wu ZF, Qiao XT, Bao L, Merajver SD: RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia 2: 418-425, 2000
10. Mira JP, Benard V, Groffen J, Sanders LC, Knaus UG: Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway. Proc Natl Acad Sci USA 97: 185-189, 2000
11. Schnelzer A, Prechtel D, Knaus U, Dehne K, Gerhard M, Graeff H, Harbeck N, Schmitt M, Lengyel E: Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene 19: 3013-3020, 2000
12. Tao W, Pennica D, Xu L, Kalejta RF, Levine AJ: Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1. Genes Dev 15: 1796-1807, 2001
13. Hamaguchi M, Meth JL, von Klitzing C, Wei W, Esposito D, Rodgers L, Walsh T, Welcsh P, King MC, Wigler MH: DBC2, a candidate for a tumor suppressor gene involved in breast cancer. Proc Natl Acad Sci USA 99: 13647-13652, 2002
14. Yuan BZ, Zhou X, Durkin ME, Zimonjic DB, Gumundsdottir K, Eyfjord JE, Thorgeirsson SS, Popescu NC: DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity. Oncogene 22: 445-450, 2003
15. Keely PJ, Westwick JK, Whitehead IP, Der CJ, Parise LV: Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K. Nature 390: 632-636, 1997
16. Bouzahzah B, Albanese C, Ahmed F, Pixley F, Lisanti MP, Segall JD, Condeelis J, Joyce D, Minden A, Der CJ, Chan A, Symons M, Pestell RG: Rho family GTPases regulate mammary epithelium cell growth and metastasis through distinguishable pathways. Mol Med 7: 816-830, 2001
17. Etienne-Manneville S, Hall A: Rho GTPases in cell biology. Nature 420: 629-635, 2002
18. Van Aelst L, D'Souza-Schorey C: Rho GTPases and signaling networks. Genes Dev 11: 2295-2322, 1997
19. Aspenstrom P: Effectors for the Rho GTPases. Curr Opin Cell Biol 11:95-102, 1999
20. Hall A: Rho GTPases and the actin cytoskeleton. Science 279: 509-514, 1998
21. Ridley A: Rho GTPases. Integrating integrin signaling. J Cell Biol 150: F107-F109, 2000
22. Wherlock M, Mellor H: The Rho GTPase family: a Racs to Wrchs story. J Cell Sci 115: 239-240, 2002
23. Fransson A, Ruusala A, Aspenstrom P: Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. J Biol Chem 278: 6495-6502, 2003
24. Wittinghofer F: Ras signalling. Caught in the act of the switch-on. Nature 394: 317319-317320, 1998
25. Schmidt A, Hall A: Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev 16: 1587-1609, 2002
26. Zheng Y: Db1 family guanine nucleotide exchange factors. Trends Biochem Sci 26: 724-732, 2001
27. Eva A, Aaronson SA: Isolation of a new human oncogene from a diffuse B-cell lymphoma. Nature 316: 273-275, 1985
28. Cote JF, Vuori K: Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. J Cell Sci 115: 4901-4913, 2002
29. Moon SY, Zheng Y: Rho GTPase-activating proteins in cell regulation. Trends Cell Biol 13: 13-22, 2003
30. Boguski MS, McCormick F: Proteins regulating Ras and its relatives. Nature 366: 643-654, 1993
31. Lamarche N, Hall A: GAPs for rho-related GTPases. Trends Genet 10: 436-440, 1994
32. Olofsson B: Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. Cell Signal 11: 545-554, 1999
33. Fukumoto Y, Kaibuchi K, Hori Y, Fujioka H, Araki S, Ueda T, Kikuchi A, Takai Y: Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins, ras p21-like small GTP-binding proteins. Oncogene 5: 1321-1328, 1990
34. Leonard D, Hart MJ, Platko JV, Eva A, Henzel W, Evans T, Cerione RA: The identification and characterization of a GDP-dissociation inhibitor (GDI) for the CDC42Hs protein. J Biol Chem 267: 22860-22868, 1992
35. Hart MJ, Maru Y, Leonard D, Witte ON, Evans T, Cerione RA: A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs. Science 258: 812-815, 1992
36. Nomanbhoy TK, Leonard DA, Manor D, Cerione RA: Investigation of the GTP-binding/GTPase cycle of Cdc42Hs using extrinsic reporter group fluorescence. Biochem 35: 4602-4608, 1996
37. Keep NH, Barnes M, Barsukov I, Badii R, Lian LY, Segal AW, Moody PC, Roberts GC: A modulator of rho family G proteins, rhoGDI, binds these G proteins via an immunoglobulin-like domain and a flexible N-terminal arm. Structure 5: 623-633, 1997
38. Gosser YQ, Nomanbhoy TK, Aghazadeh B, Manor D, Combs C, Cerione RA, Rosen MK: C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases. Nature 387: 814-819, 1997
39. Hoffman GR, Nassar N, Cerione RA: Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell 100: 345-356, 2000
40. Symons M, Settleman J: Rho family GTPases: more than simple switches. Trends Cell Biol 10: 415-419, 2000
41. Schmidt A, Hall A: Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev 16: 1587-1609, 2002
42. Lemmon MA, Ferguson KM, Abrams CS: Pleckstrin homology domains and the cytoskeleton. FEBS Lett 513: 71-76, 2002
43. Habets GG, Scholtes EH, Zuydgeest D, van der Kammen RA, Stam JC, Berns A, Collard JG: Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell 77: 537-549, 1994
44. Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG: A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature 375: 338-340, 1995
45. Olson MF, Pasteris NG, Gorski JL, Hall A: Faciogenital dysplasia protein (FGD1) and Vav, two related proteins required for normal embryonic development, are upstream regulators of Rho GTPases. Curr Biol 6: 1628-1633, 1996
46. Zheng Y, Glaven JA, Wu WJ, Cerione RA: Phosphatidylinositol 4,5-bisphosphate provides an alternative to guanine nucleotide exchange factors by stimulating the dissociation of GDP from Cdc42Hs. J Biol Chem 271: 23815-23819, 1996
47. Han J, Das B, Wei W, Aelst LV, Mosteller RD, Khosravi-Far R, Westwick JK, Der CJ, Broek D: Lck regulates Vav activation of members of the Rho family of GTPases. Mol Cell Biol 17: 1346-1353, 1997
48. Abe K, Rossman KL, Liu B, Ritola KD, Chiang D, Campbell SL, Burridge K, Der CJ: Vav2 is an activator of Cdc42, Rac1, and RhoA. J Biol Chem 275: 10141-10149, 2000
49. Liu X, Wang H, Eberstadt M, Schnuchel A, Olejniczak ET, Meadows RP, Schkeryantz JM, Janowick DA, Harlan JE, Harris EA, Staunton DE, Fesik SW: NMR structure and mutagenesis of the N-terminal Db1 homology domain of the nucleotide exchange factor Trio. Cell 95: 269-277, 1998
50. Aghazadeh B, Zhu K, Kubiseski TJ, Liu GA, Pawson T, Zheng Y, Rosen MK: Structure and mutagenesis of the Db1 homology domain. Nat Struct Biol 5: 1098-1107, 1998
51. Aghazadeh B, Lowry WE, Huang XY, Rosen MK: Structural basis for relief of autoinhibition of the Db1 homology domain of proto-oncogene Vav by tyrosine phosphorylation. Cell 102: 625-633, 2000
52. Soisson SM, Nimnual AS, Uy M, Bar-Sagi D, Kuriyan J: Crystal structure of the Db1 and pleckstrin homology domains from the human Son of sevenless protein. Cell 95: 259-268, 1998
53. Worthylake DK, Rossman KL, Sondek J: Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature 408: 682-688, 2000
54. Rossman KL, Worthylake DK, Snyder JT, Siderovski DP, Campbell SL, Sondek J: A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange. EMBO J 21: 1315-1326, 2002
55. Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J: Structural basis for the selective activation of Rho GTPases by Db1 exchange factors. Nat Struct Biol 9: 468-475, 2002
56. Karnoub AE, Worthylake DK, Rossman KL, Pruitt WM, Campbell SL, Sondek J, Der CJ: Molecular basis for Rac1 recognition by guanine nucleotide exchange factors. Nat Struct Biol 8: 1037-1041, 2001
57. van den Berghe N, Cool RH, Wittinghofer A: Discriminatory residues in ras and rap for guanine nucleotide exchange factor recognition. J Biol Chem 274: 11078-11085, 1999
58. Gao Y, Xing J, Streuli M, Leto TL, Zheng Y: Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors. J Biol Chem 276: 47530-47541, 2001
59. Arthur WT, Ellerbroek SM, Der CJ, Burridge K, Wennerberg K: XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. J Biol Chem 277: 42964-42972, 2002
60. Feig LA: Tools of the trade: use of dominant-inhibitory mutants of Ras-family GTPases. Nat Cell Biol 1: E25-E27, 1999
61. Davies SP, Reddy H, Caivano M, Cohen P: Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J 351: 95-105, 2000
62. Symons M, Derry JM, Karlak B, Jiang S, Lemahieu V, McCormick F, Francke U, Abo A: Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 84: 723-734, 1996
63. Cheng L, Rossman KL, Mahon GM, Worthylake DK, Korus M, Sondek J, Whitehead IP: RhoGEF specificity mutants implicate RhoA as a target for Dbs transforming activity. Mol Cell Biol 22: 6895-6905, 2002
64. Bishop AL, Hall A: Rho GTPases and their effector proteins. Biochem J 348(Pt 2): 241-255, 2000
65. Wittinghofer A, Nassar N: How Ras-related proteins talk to their effectors. Trends Biochem Sci 21: 488-491, 1996
66. Westwick JK, Lambert QT, Clark GJ, Symons M, Van Aelst L, Pestell RG, Der CJ: Rac regulation of transformation, gene expression, and actin organization by multiple, PAK-independent pathways. Mol Cell Biol 17: 1324-1335, 1997
67. phox in complex with Rac GTP. Mol Cell 6: 899-907, 2000
68. Maesaki R, Ihara K, Shimizu T, Kuroda S, Kaibuchi K, Hakoshima T: The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1. Mol Cell 4: 793-803, 1999
69. Self AJ, Paterson HF, Hall A: Different structural organization of Ras and Rho effector domains. Oncogene 8: 655-661, 1993
70. Diekmann D, Nobes CD, Burbelo PD, Abo A, Hall A: Rac GTPase interacts with GAPs and target proteins through multiple effector sites. EMBO J 14: 5297-5305, 1995
71. Fujisawa JL, Madaule P, Ishizaki T, Watanabe G, Bito H, Saito Y, Hall A, Narumiya S: Different regions of Rho determine Rho-selective binding of different classes of Rho target molecules. J Biol Chem 273: 18943-18949, 1998
72. Bae CD, Min DS, Fleming IN, Exton JH: Determination of interaction sites on the small G protein RhoA for phospholipase D. J Biol Chem 273: 11596-11604, 1998
73. Sahai E, Alberts AS, Treisman R: RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. EMBO J 17: 1350-1361, 1998
74. Mott HR, Owen D, Nietlispach D, Lowe PN, Manser E, Lim L, Laue ED: Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK. Nature 399: 384-388, 1999
75. Abdul-Manan N, Aghazadeh B, Liu GA, Majumdar A, Ouerfelli O, Siminovitch KA, Rosen MK: Structure of Cdc42 in complex with the GTPase-binding domain of the 'Wiskott-Aldrich syndrome' protein. Nature 399: 379-383, 1999
76. Morreale A, Venkatesan M, Mott HR, Owen D, Nietlispach D, Lowe PN, Laue ED: Structure of Cdc42 bound to the GTPase binding domain of PAK. Nat Struct Biol 7: 384-388, 2000
77. Burbelo PD, Drechsel D, Hall A: A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases. J Biol Chem 270: 29071-29074, 1995
78. Morreale A, Venkatesan M, Mott HR, Owen D, Nietlispach D, Lowe PN, Laue ED: Structure of Cdc42 bound to the GTPase binding domain of PAK. Nat Struct Biol 7: 384-388, 2000
79. Valencia A, Chardin P, Wittinghofer A, Sander C: The ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry 30: 4637-4648, 1991
80. Freeman JL, Abo A, Lambeth JD: Rac 'Insert Region' is a novel effector region that is implicated in the activation of NADPH oxidase, but not PAK65. J Biol Chem 271: 19794-19801, 1996
81. phox. J Biol Chem 272: 18834-18841, 1997
82. Wu WJ, Leonard DA, Cerione RA, Manor D: Interaction between Cdc42Hs and RhoGDI is mediated through the Rho insert region. J Biol Chem 26153-26158, 1997
83. Walker SJ, Brown HA: Specificity of Rho insert-mediated activation of phospholipase D1. J Biol Chem 277: 26260-26267, 2002
84. Wu WJ, Lin R, Cerione RA, Manor D: Transformation activity of Cdc42 requires a region unique to Rho-related proteins. J Biol Chem 273: 16655-16658, 1998
85. Zong H, Raman N, Mickelson-Young LA, Atkinson SJ, Quilliam LA: Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation. J Biol Chem 274: 4551-4560, 1999
86. Karnoub AE, Der CJ, Campbell SL: The insert region of Rac1 is essential for membrane ruffling but not cellular transformation. Mol Cell Biol 21: 2847-2857, 2001
87. Joneson T, Bar-Sagi D: A Rac1 effector site controlling mitogenesis through superoxide production. J Biol Chem 273: 17991-17994, 1998
88. Joneson T, Bar-Sagi D: Suppression of Ras-induced apoptosis by the Rac GTPase. Mol Cell Biol 19: 5892-5901, 1999
89. Zohar M, Teramoto H, Katz BZ, Yamada KM, Gutkind JS: Effector domain mutants of Rho dissociate cytoskeletal changes from nuclear signaling and cellular transformation. Oncogene 17: 991-998, 1998
90. Joneson T, McDonough M, Bar-Sagi D, Van Aelst L: RAC regulation of actin polymerization and proliferation by a pathway distinct from Jun kinase. Science 274: 1374-1376, 1996
91. Lamarche N, Tapon N, Stowers L, Burbelo PD, Aspenstrom P, Bridges T, Chant J, Hall A: Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade. Cell 87: 519-529, 1996
92. Sahai E, Alberts AS, Treisman R: RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. EMBO J 17: 1350-1361, 1998
93. Khosravi-Far R, White MA, Westwick JK, Solski PA, Chrzanowska-Wodnicka M, Van Aelst L, Wigler MH, Der CJ: Oncogenic Ras activation of Raf/mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation. Mol Cell Biol 16: 3923-3933, 1996
94. Reeder MK, Serebriiskii IG, Golemis EA, Chernoff J: Analysis of small GTPase signaling pathways using p21-activated kinase mutants that selectively couple to Cdc42. J Biol Chem 276: 40606-40613, 2001
95. Zugaza JL, Lopez-Lago MA, Caloca MJ, Dosil M, Movilla N, Bustelo XR: Structural determinants for the biological activity of Vav proteins. J Biol Chem 277: 45377-45392, 2002
96. Buchsbaum RJ, Connolly BA, Feig LA: Regulation of p70 S6 kinase by complex formation between the Rac guanine nucleotide exchange factor (Rac-GEF) Tiam1 and the scaffold spinophilin. J Biol Chem 278: 18833-18841, 2003
97. Buchsbaum RJ, Connolly BA, Feig LA: Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for the p38 mitogen-activated protein kinase cascade. Mol Cell Biol 22: 4073-4085, 2002
98. Zhou K, Wang Y, Gorski JL, Nomura N, Collard J, Bokoch GM: Guanine nucleotide exchange factors regulate specificity of downstream signaling from Rac and Cdc42. J Biol Chem 273: 16782-16786, 1998
99. Meller N, Irani-Tehrani M, Kiosses WB, Del Pozo MA, Schwartz MA: Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nat Cell Biol 4: 639-647, 2002
100. Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, Macara IG, Madhani H, Fink GR, Ravichandran KS: Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol 4: 574-582, 2002
101. Gardiner EM, Pestonjamasp KN, Bohl BP, Chamberlain C, Hahn KM, Bokoch GM: Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis. Curr Biol 12: 2029-2034, 2002
102. Itoh RE, Kurokawa K, Ohba Y, Yoshizaki H, Mochizuki N, Matsuda M: Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol Cell Biol 22: 6582-6591, 2002
103. Kraynov VS, Chamberlain C, Bokoch GM, Schwartz MA, Slabaugh S, Hahn KM: Localized Rac activation dynamics visualized in living cells. Science 290: 333-337, 2000
104. Hirshberg M, Stockley RW, Dodson G, Webb MR: The crystal structure of human Rac1, a member of the Rho-family complexed with a GTP analogue. Nat Struct Biol 4: 147-152, 1997