Oncogene-lnitiated Aberrant Signaling Engenders the Metastatic Phenotype: Synergistic Transcription Factor Interactions are Targets for Cancer Therapy

Critical Reviews in Oncogenesis

Volumn 7, Issue 3-4, 1996, Pages 261-291

  Denhardt, David T ^a,b  

^a RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^b RUTGERS UNIVERSITY   (United States)

Author keywords

MAPK; P21GTPase; Protein phosphorylation; Ras; Rho; Signal transduction

Indexed keywords

ARTICLE; GENE EXPRESSION REGULATION; GENE TARGETING; HUMAN; METASTASIS; ONCOGENE; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION;

ANIMALS; GENE THERAPY; GENES, FOS; GTP PHOSPHOHYDROLASES; GTP-BINDING PROTEINS; HUMANS; MUTATION; NEOPLASM METASTASIS; ONCOGENES; PHOSPHORYLATION; RHO GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION; STRESS; TRANSCRIPTION FACTOR AP-1; TRANSCRIPTION FACTORS;

EID: 0030390037     PISSN: 08939675     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevOncog.v7.i3-4.70     Document Type: Article

References (238)

1. Abate, C., L. Patel, F. J. Rauscher III, and T. Curran: Redox regulation of Fos and Jun DNA-binding activity in vitro. Science, 249:1157-1161 (1990).
2. GAP and neurofibromin. J. Biol. Chem., 271:16409-16415 (1996).
3. Akasaka, K., M. Tamada, F. Wang, K.-I. Kariya, F. Shima, A. Kikuchi, M. Yamamoto, M. Shirouzu, S. Yokoyama, and T. Kataoka: Differential structural requirements for interaction of Ras protein with its distinct downstream effectors. J. Biol. Chem., 271:5353-5360 (1996).
4. Alarcon, R. M., B. A. Rupnow, T. G. Graeber, S. J. Knox, and A. J. Giaccia: Modulation of c-Myc activity and apoptosis in vivo. Cancer Res., 56:4315-4319 (1996).
5. ras mutants and cEts2 activate the cyclin D1 promoter through distinguishable regions. J. Biol. Chem., 270:23589-23597 (1995).
6. Amano, M., K. Chihara, K. Kimura, Y. Fukata, N. Nakmura, Y. Matsuura, and K. Kaibuchi: Formation of actin stress fibers and focal adhesions enhanced by rho-kinase. Science, 275:1308-1311 (1997).
7. Amano, M., H. Mukai, Y. Ono, K. Chihara, T. Matsui, Y. Hamajima, K. Okawa, A. Iwamatsu, and K. Kaibuchi: Identification of a putative target for Rho as the serinethreonine kinase protein kinase N. Science, 271:648-650 (1996).
8. Aronheim, A., D. Engelberg, N. Li, N. Al-Alawi, J. Schlessinger, and M. Karin: Membrane targeting of the nucleotide exchange factor SOS is sufficient for activating the Ras signaling pathway. Cell, 78:949-961 (1994).
9. Ayer, D. E., C. D. Laherty, Q. A. Lawrence, A. P. Armstrong, and R. N. Eisenman: Mad proteins contain a dominant transcription repression domain. Mol. Cell. Biol., 16:5772-5781 (1996).
10. Baeuerle, P. A. and D. Baltimore: NF-κB: ten years after. Cell, 87:13-20 (1996).
11. Bains, N. P. S., J. A. Wilce, K. H. Heuer, M. Tunstall, J. P. Mackay, M. R. Bennett, A. S. Weiss, and G. F. King: Zipping up transcription factors: rational design of anti-Jun and anti-Fos peptides. J. Peptide Sci., 4:67-77 (1997).
12. Baldwin, A. S. Jr.: The NF-κB and 1κB proteins: new discoveries and insights. Annu. Rev. Immunol., 14:649-681 (1996).
13. Barford, D.: Protein phosphatases. Curr. Opin. Struct. Biol., 5:728-734 (1995).
14. Barone, M. V. and S. A. Courtneidge: Myc but not Fos rescue of PDGF signaling block caused by kinase-inactive Src. Nature, 378:509-512 (1995).
15. Behrend, E. I., A. M. Craig, S. M. Wilson, D. T. Denhardt, and A. F. Chambers: Reduced malignancy of ras-transformed NIH 3T3 cells expressing antisense osteopontin RNA. Cancer Res., 54:832-837 (1994).
16. Bello-Fernandez, C., G. Packham, and J. L. Cleveland: The ornithine decarboxylase gene is a transcriptional target of c-Myc. Proc. Natl. Acad. Sci. U.S.A., 90:7804-7808 (1993).
17. Besser, D., M. Presta, and Y. Nagamine: Elucidation of a signaling pathway induced by FGF-2 leading to uPA gene expression in NIH3T3 fibroblasts. Cell Growth Differen., 6:1009-1017 (1995).
18. Blank, J. L., P. Gerwins, E. M. Elliott, S. Sather, and G. L. Johnson: Molecular cloning of MEKK 2 and 3. J. Biol. Chem., 271:5361-5368 (1996).
19. Bogoyevitch , M. A., A. J. Ketterman, and P. H. Sugden: Cellular stresses differentially activate c-Jun N-terminal protein kinases and extracellular signal-related protein kinases in cultured ventricular myocytes. J. Biol. Chem., 270:29710-29717 (1995).
20. Bokemeyer, D., A. Sorokin, M. Yan, N. G. Ahn, D. J. Templeton, and M. J. Dunn: Induction of mitogen-activated protein kinase phosphatase 1 by the stress-activated protein kinase signaling pathway but not by extracellular signal-regulated kinase in fibroblasts. J. Biol. Chem., 271:639-642 (1996).
21. Bokoch, G. M.: Interplay between Ras-related and heterotrimeric GTP binding proteins: lifestyles of the big and litue. FASEB J., 10:1290-1295 (1996).
22. Borther, D. M., S. J. Langer, and M. C. Ostrowski: Nonnuclear oncogenes and the regulation of gene expression in transformed cells. Crit. Rev. Oncogen., 4:137-160 (1993).
23. Bourmeyster, N. and P. V. Vignais: Phosphorylation of Rho GDI stabilizes the Rho A-Rho GDI complex in neutrophil cytosol. Biochem. Biophys. Res. Comm., 218:54-60 (1996).
24. Bradford, A. P., K. E. Conrad, C. Wasylyk, B. Wasylyk, and A. Gutierrez-Hartmann: Functional interaction of c-Ets-1 and GHF-l/Pit-1 mediates ras activation of pituitary-specific gene expression: mapping of the essential c-Ets-1 domain. Mol. Cell. Blol., 15:2849-2857 (1995).
25. Bradford, A. P., K. E. Conrad, P. H. Tran, M. C. Ostrowski, and A. Guttierrez-Hartman: GHF-l/Pit-1 functions as a cell-specific integrator of Ras signaling by targeting the Ras pathway to a composite Ets-1/GHF-1 response element. J. Biol. Chem., 271:24639-24648 (1996).
26. Brill, S., S. Li, C. W. Lyman, D. M. Church, J. J. Wasmuth, L. Weissbach, A. Bernards, and A. J. Snijders: The ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases. Mol. Cell. Biol., 16:4869-4878 (1996).
27. Brown, K., S. Gerstberger, L. Carlson, G. Franzoso, and U. Siebenlist: Control of IκB proteolysis by site-specific signal-induced phosphorylation. Science, 267:1485-1488 (1995).
28. Bruder, J. T., G. Heidecker, and U. R. Rapp: Serum-, TPA, and Ras-induced expression from Ap-l/Etsdriven promoters requires Raf-1 kinase. Genes Dev., 6:545-556 (1992).
29. Bryant, S. S., S. Briggs, T. E. Smithgall, G. A. Martin, F. McCormick, J.-H. Chang, S. J. Parsons, and R. Jove: Two SH2 domains of p120 Ras GTPase-activating protein bind synergistically to tyrosine phosphorylated p190 Rho GTPase-activating protein. J. Biol. Chem., 270:17947-17952 (1995).
30. Burbelo, P. D., D. Drechsel, and A. Hall: A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac Gpases. J. Biol. Chem., 270:29071-29074 (1995).
31. Byrne, J. L., H. F. Paterson, and C. J. Marshall: p21Ras activation by the guanine nucleotide exchange factor Sos requires the Sps/Grb2 interaction and a second ligand-dependent signal involving the Sos N-terminus. Oncogene, 13:2055-2065 (1996).
32. Cantor, S. B., T. Urano, and L. A. Feig: Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases. Mol. Cell. Biol., 15:4578-4584 (1995).
33. Cavigelli, M., F. Dolfi, F.-X. Claret, and M. Karin: Induction of c-fos expression through JNK-mediated TCF-Elkl phosphorylation. EMBO J., 14:5957-5964 (1995).
34. Cerione, R. A. and Y. Zheng: The Dbl family of oncogenes. Curr. Opin. Cell Biol., 8:216-222 (1996).
35. Chambers, A. F. and A. B. Tuck: Ras-responsive genes and tumor metastasis. Crit. Rev. Oncogen., 4:95-114 (1993).
36. Chant, J. and L. Stowers: GTPase cascades choreographing cellular behavior: movement, morphogenesis and more. Cell, 81:1-4 (1995).
37. Chen, Z., J. Hagler, V. J. Palombella, F. Melandri, D. Scherer, D. Ballard, and T. Maniatis: Signal-induced site-specific phosphorylation targets IκBα to the ubiquitin-proteasome pathway. Genes Dev., 9:1586-1597 (1995).
38. Chen, Z. J., L. Parent, and T. Maniatis: Site-specific phosphorylation of IκBα by a novel ubiquitination-dependent protein kinase activity. Cell, 84:853-862 (1996).
39. Chen, P., H. Xie, and A. Wells: Mitogenic signaling from the EGF receptor is attenuated by a phospholipase C-γ/ protein kinase C feedback mechanism. Mol. Biol. Cell, 7:871-881 (1996).
40. Chuang, T.-H., X. Xu, V. Kaartinen, N. Heisterkamp, J. Groffen, and G. M. Bokoch: Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein family. Proc. Natl. Acad. Sci. U.S.A., 92:10282-10286 (1995).
41. Claret, F.-X., M. Hibi, S. Dhut, T. Toda, and M. Karin: A new group of conserved coactivators that increae the specificity of AP-1 transcription factors. Nature, 383:453-457 (1996).
42. Clark, A. R. and K. Docherty: Negative regulation of transcription in eukaryotes. Biochem. J., 296:521-541 (1993).
43. Clark, G. J., J. K. Westwick, and C. J. Der: p120 GAP modulates Ras activation of Jun kinases and transformation. J. Biol. Chem., 272:1677-1681 (1997).
44. Cobb, M. H. and E. J. Goldsmith: How MAP kinases are regulated. J. Biol. Chem., 270:14843-14846 (1995).
45. Coffer, P., M. de Jonge, A. Mettouchi, B. Binetruy, J. Ghysdael, and W. Kruijer: junB promoter regulation: Ras mediated transactivation by c-Ets-1 and c-Ets-2. Oncogene, 9:911-921 (1994).
46. Cowley, S., H. Paterson, P. Kemp, and C. J. Marshall: Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH3T3 cells. Cell, 77:841-852 (1994).
47. Crepieux, P., J. Coll, and D. Stehelin: The Ets family of proteins: weak modulators of gene expression in quest for transcriptional partners. Crit. Rev. Oncogen., 5:615-638 (1994).
48. Crespo, P., K. E. Schuebel, A. A. Ostrom, J. S. Gutkind, and X. R. Bustelo: Phosphotyrosine-dependent activation of Rac-1GDP/GTP exchange by the vav proto-oncogene product. Nature, 385:169-172 (1997).
49. Cuenda, A., P. Cohen, V. Buee-Scherrer, and M. Goedert: Activation of SAPK3 by cytokines and cellular stresses is mediated via SAPKK3 (MKK6): comparison of the specificities of SAPK3 and SAPK2 (RK/p38). EMBO J., 16:295-305 (1997).
50. D'Arcangelo, G., R. Habas, S. Wang, S. Halegoua, and S. R. J. Salton: Activation of codependent transcription factors is required for transcriptional induction of the vgf gene by nerve growth factor and Ras. Mol. Biol. Cell., 16:4621-4631 (1996).
51. Deng, T. and M. Karin: c-Fos transcriptional activity stimulated by H-ras-activated protein kinase distinct from INK and ERK. Nature, 371:171-175 (1994).
52. Denhardt, D. T.: Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell: the potential for multiplex signaling. Biochem. J., 318:729-747 (1996).
53. Denhardt, D. T. and A. F. Chambers: Overcoming obstacles to metastasis-Defenses against host defenses: osteopontin (OPN) as a shield against attack by cytotoxic host cells. J. Cell. Biochem., 56:48-51 (1994).
54. Denhardt, D. T. and X. Guo: Osteopontin: a protein with diverse functions. FASEB J., 7:1475-1482 (1993).
55. phox and regulation of phagocytic NADPH oxidase activity. Science, 265:531-534 (1994).
56. Dohlman, H. G. and J. Thorner: RGS proteins and signaling by heterotrimeric G proteins. J. Biol. Chem., 272:3871-3874 (1997).
57. Drugan, J. K., R. Khosravi-Far, M. A. White, C. J. Der, Y.-J. Sung, Y.-W. Hwang, and S. L. Campbell: Ras interaction with two distinct binding domains in Raf-1 may be required for Ras transformation. J. Biol. Chem., 271:233-237 (1996).
58. Ellinger-Ziegelbauer, H., K. Brown, K. Kelly, and U. Siebenlist: Direct activation of SAPK and ERK pathways by an inducible MEKK3 derivative. J. Biol. Chem., 272:2668-2674 (1997).
59. mapk but not ERK2. J. Biol. Chem., 271:24788-24793 (1996).
60. Feig, L. A., T. Urano, and S. Cantor: Evidence for a Ras/ Ral signaling cascade. Trends Biochem. Sci., 21:438-441 (1996).
61. Feng, B., E. E. Rollo, and D. T. Denhardt: Osteopontin may facilitate metastasis by protecting cells from macrophage NO-mediated cytotoxicity: evidence from cell lines down-regulated for OPN expression by a targeted ribozyme. Clin. Exp. Metastasis, 13:453-462 (1995).
62. Felts, S. J., E. S. Stoflet, C. T. Eggers, and M. J. Getz: Tissue factor gene transcription in serum-stimulated fibroblasts is mediated by recruitment of c-Fos into specific AP-1 DNA-binding complexes. Biochemistry, 34:12355-12362 (1995).
63. 129 is required for the cAMP-mediated control of gene expression. J. Biol. Chem., 269:32187-32193 (1994).
64. Fleming, I. N., C. M. Elliott, and J. H. Exton: Differential translocation of Rho family GTPases by lysophosphatidic acid, endothelin-1, and platelet-derived growth factor. J. Biol. Chem., 271:33067-33073 (1996).
65. Freeman, J. L., A. Abo, and J. D. Lambeth: 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).
66. Frost, J. A., S. Xu, M. R. Hutchison, S. Marcus, and M. H. Cobb: Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members. Mol. Cell. Biol., 16:3707-3713 (1996).
67. Gardner, H. A. R., B. Berse, and D. R. Senger: Specific reduction in osteopontin synthesis by antisense RNA inhibits the tumorigenicity of transformed Ratl fibroblasts. Oncogene, 9:2341-2326 (1994).
68. Gerwin, P., J. L. Blank, and G. L. Johnson: Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the cJun amino terminal kinase pathway. J. Biol. Chem., 272:8288-8295 (1997).
69. Gilmore, T. D., M. Koedood, K. A. Piffat, and D. W. White: Rel/NF-κB/lKB proteins and cancer. Oncogene, 13:1367-1378 (1996).
70. Ginty, D. D., A. Bonni, and M. E. Greenberg: Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell, 77:713-725 (1994).
71. Giovane, A., A. Pintzas, S.-M. Maira, P. Sobieszczuk, and B. Wasylyk: Net, a new ets transcription factor that is activated by Ras. Genes Dev., 8:1502-1513 (1994).
72. Gotoh, N., M. Toyoda, and M. Shibuya: Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein tyrosine kinase activation. Mol. Cell. Biol., 17:1824-1831 (1997).
73. Grimm, S. and P. A. Baeuerle: The inducible transcription factor NF-κB: structure-function relationship of its protein subunits. Biochem. J., 290:297-308 (1993).
74. Guo, X., Y. P. Zhang, D. A. Mitchell, D. T. Denhardt, and A. F. Chambers: Identification of a ros-activated enhancer in the mouse osteopontin promoter and its interaction with a putative Ets-related transcription factor whose activity correlates with the metastatic potential of the cell. Mol. Cell. Biol., 15:476-487 (1995).
75. Gupta, S., D. Campbell, B. Derijard, and R. J. Davis: Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science, 267:389-393 (1995).
76. Gupta, S., T. Barrett, A. J. Whitmarsh, J. Cavanagh, H. K. Sluss, B. Derijard, and R. J. Davis: Selective interaction of INK protein kinase isoforms with transcription factors. EMBO J., 15:2760-2770 (1996).
77. Gutman, A. and B. Wasylyk: The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites. EMBO J., 9:2241-2246 (1990).
78. Han, J., J.-D. Lee, L. Bibbs, and R. J. Ulevitch: A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science, 265:808-811 (1994).
79. Hawker, K. L., J. K. Vass, and B. W. Ozanne: Isolation of novel, transcriptionally active AP-1 binding sites: implications for cellular transformation. Oncogene, 13:283-292 (1996).
80. Herman, W. H. and M. S. Simonson: Nuclear signaling by endothelin-1: a ras pathway for activation of the c-fos serum response element. J. Biol. Chem., 270:11654-11661 (1995).
81. Herrmann, C., G. Horn, M. Spaargaren, and A. Wittinghofer: Differential interaction of the RAS family GTP-binding proteins H-Ras, Rap1A, and R-Ras with the putative effector molecules Raf kinase and Ral-guanine nucleotide exchange factor. J. Biol. Chem., 271:6794-6800 (1996).
82. Hill, C. S. and R. Treisman: Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell, 80:199-211 (1995).
83. Hill, C. S., J. Wynne, and R. Treisman: The Rho family GTPases RhosA, Rac1, and Cdc42Hs regulate transcriptional activation by SRF. Cell, 81:1159-1170 (1995).
84. Hirai, S.-I., M. Izawa, S.-I. Osada, G. Spyrou, and S. Ohno: Activation of the JNK pathway by distantiy related protein kinases, MEKK and MUK. Oncogene, 12:641-650 (1996).
85. Hirano, M., S.-I. Osada, T. Aoki, S. Hirai, M. Hosaka, J.-I. Inoue, and S. Ohno: MEK kinase is involved in tumor necrosis factor α-induced NF-κB activation and degradation of IκB-α. J. Biol. Chem., 271:13234-13238 (1996).
86. Hori, Y., J. F. Beeler, K. Sakaguchi, M. Tachibana, and T. Miki: A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways. EMBO J., 13:4776-4786 (1994).
87. Howard, P. W. and R. A. Maurer: A composite Ets/Pit-1 binding site in the prolactin gene can mediate transcriptional responses to multiple signal transduction pathways. J. Biol Chem., 270:20930-20936 (1995).
88. Huang, C., P. C. Schmid, W.-Y. Ma, H. H. O. Schmid, and Z. Dong: Phosphatidylinositol-3-kinase is necessary for 12-O-tetradecanoylphorbol-13-acetate-induced cell transformation and AP-1 activation. J. Biol. Chem., 272:4187-4194 (1997).
89. Hunter, T.: When is a lipid kinase not a lipid kinase? When it is a protein kinase. Cell, 83:1-4 (1995).
90. Hunter, T.: Oncoprotein networks. Cell, 88:333-346 (1997).
91. Hyvonen, M., M. J. Macias, M. Nilges, H. Oschkinat, M. Saraste, and M. Wilmanns: Structure of the binding site for inositol phosphates in a PH domain. EMBO J., 14:4676-4685 (1995).
92. lordanov, M., K. Bender, T. Ade, W. Schmid, C. Sachsenmaier, K. Engel, M. Gaestel, H. J. Rahmsdorf, and P. Herrlich: CREB is activated by UVC through a p38/HOG-l-dependent kinase. EMBO J., 16:1009-1022 (1997).
93. Ishizaki, T., M. Maekawa, K. Fujisawa, K. Okawa, A. Iwamatsu, A. Fujita, N. Watanabe, Y. Saito, A. Kakizuka, N. Morii, and S. Narumiya: The small GTP-binding protein Rho binds to and activates a 160 kDa ser/thr protein kinase homologous to myotonic dystrophy kinase. EMBO J., 15:1885-1893 (1996).
94. Jaaro, H., H. Rubinfeld, T. Hanoch, and R. Seger: Nuclear translocation of mitogen-activated protein kinase kinase (MEK1) in response to mitogenic stimulation. Proc. Natl. Acad. Sci. U.S.A., 94:3742-3747 (1997).
95. Janicke, R. U., X. Y. Lin, F. H. H. Lee, and A. G. Porter: Cyclin D3 sensitizes tumor cells to tumor necrosis factor-induced cMyc-dependent apoptosis. Mol. Cell. Biol., 16:5245-5253 (1996).
96. Janknecht, R. and T. Hunter: A growing coactivator network. Science, 383:22-23 (1996).
97. Janknecht, R. and T. Hunter: Activation of the Sap-la transcription factor by the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase. J. Biol. Chem., 272:4219-4224 (1997a).
98. Janknecht, R. and T. Hunter: Convergence of MAP kinase pathways on the ternary complex factor Sap-1a. EMBO J., 16:1620-1627 (1997b).
99. Janknecht, R., D. Monte, J.-L. Baert, and Y. de Launoit: The ETS-related transcription factor ERM is a nuclear target of signaling cascades involving MAPK and PKA. Oncogene, 13:1745-1754 (1996).
100. Janknecht, R. and A. Nordheim: Gene regulation by Ets proteins. Biochim. Biophys. Acta, 1155:346-356 (1993).
101. Janosch, P., M. Scheuerer, T. Seitz, P. Reim, M. Eulitz, M. Brielmeier, W. Kolch, J. M. Sedivy, and H. Mischak: Characterization of IκB kinases. J. Biol. Chem., 271:13868-13874 (1996).
102. Jelinek, T., P. Dent, T. W. Sturgill, and M. J. Weber: Rasinduced activation of Raf-1 is dependent on tyrosine phosphorylation. Mol. Cell. Biol., 16:1027-1034 (1996).
103. Johnson, N. L., A. M. Gardner, K. M. Diener, C. A. Lange-Carter, J. Gleavy, M. B. Jarpe, A. Minden, M. Karin, L. I. Son, and G. L. Johnson: Signal transduction pathways regulated by mitogen-activated/extracellular response kinase kinase kinase induce cell death. J. Biol. Chem., 271:3229-3237 (1996a).
104. Johnson, R., B. Spiegelman, D. Hanahan, and R. Wisdom: Cellular transformation and malignancy induced by RAS require c-Jun. Mol. Cell. Biol., 16:4504-4511 (1996b).
105. Joneson, T., M. McDonough, D. Bar-Sagi, and L. van Aelst: RAC regulation of actin polymerization and proliferation by a pathway distinct from Jun kinase. Science, 274:1374-1376 (1996).
106. Kallunki, T., T. Deng, M. Hibi, and M. Karin: c-Jun can recruit JNK to phosphorylate dimerization partners via specific docking interactions. Cell, 87:929-939 (1996).
107. Karin, M: The regulation of Ap-1 activity by mitogen-activated protein kinases. J. Biol. Chem., 270:16483-16486 (1995).
108. Katzav, S., G. Packham, M. Sutherland, P. Aroca, E. Santos, and J. L. Cleveland: Vav and Ras induce fibroblast transformation by overlapping signaling pathways which require c-Myc function. Oncogene, 11:1079-1088 (1995).
109. Kauffmann-Zeh, A., P. Rodriguez-Viciana, E. Ulrich, C. Gilbert, P. Coffer, J. Downward, and G. Evan: Suppression of c-Myc-induced apoptosis by Ras signaling through PI(3)K and PKB. Nature, 385:544-548 (1997).
110. Kavanaugh, W. M., C. W. Turck, and L. T. Williams: PTB domain binding to signaling proteins through a sequence motif containing phosphotyrosine. Science, 268:1177-1179 (1995).
111. Khosravi-Far, R. and C. J. Der: The ras signal transduction pathway. Cancer Metastasis Rev., 13:67-89 (1994).
112. Khosravi-Far, R., P. A. Solski, G. J. Clark, M. S. Kinch, and C. J. Der: Activation of Rac1, RhoA, and MAPKs is required for Ras transformation. Mol. Cell. Biol., 15:6443-6453 (1995).
113. Kieser, A., T. Steitz, H. S. Adler, P. Coffer, E. Kremmer, P. Crespo, J. S. Gutkind, D. W. Henderson, J. F. Mushinski, W. Kolch, and H. Mischak: Protein kinase C-ζ reverts v-raf transformation of NIH3T3 cells. Genes Dev., 10:1455-1466 (1996).
114. Bum, S.-H., G. G. Prive, and M. V. Milburn: Conformational switch and structural basis for oncogenic mutations of Ras proteins. In: Handbook of Experimental Pharmacology, Vol. 108/I, GTPases in Biology (B. F. Dickey and L. Birnbaumer, Eds.) Springer-Verlag Press, Berlin (1993).
115. Klippel, A., C. Reinhard, W. M. Kavanaugh, G. Apell, M.-A. Escobedo, and L. T. Williams: Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways. Mol. Cell. Biol., 16:4117-4127 (1996).
116. Kowenz-Leutz, E., G. Twamley, S. Ansieau, and A. Leutz: Novel mechanism of C/EBPβ (NF-M) transcriptional control: activation through derepression. Genes Dev., 8:2781-2791 (1994).
117. Kuroda, S., M. Fukata, K. Kobayashi, M. Nakafuku, N. Nomura, A. Iwamatsu, and K. Kaibuchi: Identification of IQGAP as a putative target for the small GTPases Cdc42 andRacl. J. Biol. Chem., 271:23363-23367 (1996).
118. Kyriakis, J. M. and J. Avruch: Sounding the alarm: protein kinase cascades activated by stress and inflammation. J. Biol. Chem., 271:24313-24316 (1996).
119. Lalli, E. and P. Sassone-Corsi: Signal transduction and gene regulation: the nuclear response to cAMP. J. Biol. Chem., 269:17359-17362 (1994).
120. PAK and the JNK/SAPK MAP kinase cascade. Cell, 87:519-529 (1996).
121. Lamb, R. F., R. F. Hennigan, K. Turnbull, K. D. Katsanakis, E. D. MacKenzie, G. D. Birnie, and B. W. Ozanne: AP-1 mediated invasion requires increased expression of the hyaluronan receptor CD44. Mol. Cell. Biol., 17:963-976 (1997).
122. Lange-Carter, C. A. and G. L. Johnson: Ras-dependent growth factor regulation of MEK kinase in PC12 cells. Science, 265:1458-1461 (1994).
123. Lee, F. S., J. Hagler, Z. J. Chen, and T. Maniatis: Activation of the IκBα kinase complex by MEKK1, a kinase of the JNK pathway. Cell, 88:213-222 (1997).
124. Lengyel, E., E. Stepp, R. Gum, and D. Boyd: Involvement of a mitogen-activated protein kinase signaling pathway in the regulation of urokinase promoter activity by c-Ha-ras. J. Biol. Chem., 270:23007-23012 (1995).
125. Leung, T., E. Manser, L. Tan, and L. Lim: A novel serine/ threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J. Biol. Chem., 270:29051-29054 (1995).
126. Li, R. and Y. Zheng: Residues of the Rho family of GTPases Rho and Cdc42 that specify sensitivity to Dbl-like guanine nucleotide exchange factors. J. Biol. Chem., 272:4671-4679 (1997).
127. Li, S. and J. M. Sedivy: Raf-1 protein kinase activates the NF-κB transcription factor by dissociating the cytoplasmic NF-κB-IκB complex. Proc. Natl. Acad. Sci. U.S.A., 90:9247-9251 (1993).
128. Liang, P., L. Averboukh, W. Zhu, and A. B. Pardee: Ras activation of genes: Mob-1 as a model. Proc. Natl. Acad. Sci. U.S.A., 91:12515-12519 (1994).
129. Liu, Z.-G., R. Baskaran, E. T. Lea-Chou, L. D. Wood, Y. Chen, M. Karin, and J. Y. J. Wang: Three distinct signaling responses by murine fibroblasts to genotoxic stress. Science, 384:273-276 (1996).
130. Livingstone, C., G. Patel, and N. Jones: ATF2 contains a phosphorylation-dependent transcriptional activation domain. EMBO J., 14:1785-1797 (1995).
131. Lotti, L. V., L. Lanfrancone, E. Migliaccio, C. Zompetta, G. Pelicci, A. E. Salcini, B. Falini, G. G. Pelicci, and M. R. Torrisi: She proteins are localized on endoplasmic reticulum membranes and are redistributed after tyrosine kinase receptor activation. Mol. Cell. Biol., 16:1946-1954(1996),
132. Lowe, P. N. and R. H. Skinner: Regulation of ras signal transduction in normal and transformed cells. Cell Signaling, 6:109-123 (1994).
133. Luscher, B., E. A. Kuenzel, E. G. Krebs, and R. N. Eisenman: Myc oncoproteins are phosphorylated by casein kinase H. EMBO J., 8:1111-1119 (1989).
134. Macara, I. G., K. M. Lounsbury, S. A. Richards, C. McKiernan, and D. Bar-Sagi: The Ras superfamily of GTPases. FASEB J., 10:625-630 (1996).
135. cdc42. Nature, 363:364-367 (1993).
136. Mansour, S. J., W. T. Matten, A. S. Hermann, J. M. Candia, S. Rong, K. Fukasawa, G. F. van de Woude, and N. G. Ahn: Transformation of mammalian cells by constitutively active Map kinase kinase. Science, 265:966-970 (1994).
137. Marais, R., Y. Light, H. F. Paterson, C. S. Mason, and C. J. Marshall: Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic Ras and tyrosine kinases. J. Biol. Chem., 272:4378-4383 (1997).
138. Marshall, M. S.: RAS target proteins in eukaryotic cells. FASEB J., 9:1311-1318 (1995).
139. Marshall, M. S.: Ras effectors. Curr. Opin. Cell Biol., 8:197-204 (1996).
140. Masquilier, D. and P. Sassone-Gorsi: Transcriptional crosstalk: Nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun. J. Biol. Chem., 267:22460-22466 (1992).
141. McCallum, S. J., W. J. Wu, and R. A. Cerione: Identification of a putative effector for Cdc42Hs with high sequence similarity to the RasGAP-related protein IQGAP1 and a Cdc42Hs binding partner with similarity to IQGAP2. J. Biol Chem., 271:21732-21737 (1996).
142. McCarthy, S. A., D. Chen, B.-S. Yang, J. J. G. Ramirez, H. Cherwinski, X.-R. Chen, M. Klagsbrun, C. A. Hauser, M. C. Ostrowski, and M. McMahon: Rapid phosphorylation of Ets-2 accompanies mitogen-activated protein kinase activation and the induction of heparin-binding epidermal growth factor gene expression by oncogenic Raf-1. Mol. Cell. Biol., 17:2401-2412 (1997).
143. McElhinny, J. A., S. A. Trushin, G. D. Bren, N. Chester, and C. V. Paya: Casein kinase II phosphorylates IκBα at S-283, S-289, S-293, and T-291 and is required for its degradation. Mol. Cell. Biol., 16:899-906 (1996).
144. McIlroy, J., D. Chen, C. Wjasow, T. Michaeli, and J. M. Backer: Specific activation of p85-p110 phosphatidyl 3-kinase stimulates DNA synthesis by ras- and p70 S6 kinase-dependent pathways. Mol. Cell. Biol., 17:248-255 (1997).
145. Michiels, F., G. G. M. Habets, J. C. Stam, R. A. van der Kammen, and J. G. Collard: A role for Rac in Tiamlinduced membrane ruffling and invasion. Nature, 375:338-340 (1995).
146. 2-terminal kinase activation: J. Cell Biol., 137:387-398 (1997).
147. Mineo, C., R. G. W. Anderson, and M. A. White: Physical association with Ras enhances activation of membranebound Raf (RafCAAX). J. Biol. Chem., 272:10345-10348 (1997).
148. Moriguchi, T., F. Toyoshima, Y. Gotoh, A. Iwamatsu, K. Me, E. Mori, N. Kuroyangi, M. Hagiwara, K. Matsumoto, and E. Nishida: Purification and identification of a major activator for p38 from osmotically shocked cells. J. Biol. Chem., 271:26981-26988 (1996).
149. Morooka, H., J. V. Bonventre, C. M. Pomba, J. M. Kyriakis, and T. Force: Ischemia and reperfusion enhance ATF2 and c-Jun bhiding to cAMP response elements and to an AP-1 binding site from the c-jun promoter. J. Biol. Chem., 270:30084-30092 (1995).
150. Moulton, K., K. Semple, H. Wu, and C. K. Glass: Cell-specific expression of the macrophage scavenger receptor gene is dependent on PU.1 and a composite AP-1/ ets motif. Mol. Cell. Biol., 14:4408-4418 (1994).
151. Nakae, K., K. Nakajima, J. Inazawa, T. Kitaoka, and T. Hirano: ERM, a PEA3 subfamily of Ets transcription factors, can cooperate with c-Jun. J. Biol. Chem., 270:23795-23800 (1995).
152. Nakajima, T., S. Kinoshita, T. Sasagawa, K. Sasaki, M. Naruto, T. Kishimoto, and S. Akira: Phosphorylation at threonine-235 by a ros-dependent mitogen-activated protein kinase cascade is essential for transcription factor NFIL6. Proc. Natl. Acad. Sci. U.S.A., 90:2207-2211 (1993).
153. rsk. Cell, 86:465-474 (1996).
154. Newton, A. C.: Protein kinase C: structure, function and regulation. J. Biol. Chem., 270:28495-28498 (1995).
155. Nilsson, M., R. Toftgard, and S. Bohm: Activated Ha-ras but not TPA induces transcription through binding sites for activating transcription factor 3/Jun and a novel nuclear factor. J. Biol. Chem., 270:12210-12218 (1995).
156. Nobes, C. D. and A. Hall: Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell, 81:53-62 (1995).
157. Dates, A. J., R. Barraclough, and P. S. Rudland: The identification of osteopontin as a metastasis-related gene product in a rodent mammary tumor model. Oncogene, 13:97-104 (1996).
158. O'Hagan, R. C., R. G. Tozer, M. Symons, F. McCormick, and J. A. Hassell: The activity of the Ets transcription factor PEA3 is regulated by two distinct MAPK cascades. Oncogene, 13:1323-1333 (1996).
159. Okazaki, K. and N. Sagata: The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH3T3 cells. EMBO J., 14:5048-5059 (1995).
160. Oldham, S. M., G. J. Clark, L. M. Gangarosa, R. J. Coffey, Jr., and C. J. Der: Activation of the Raf-1/MAP kinase cascade is not sufficient for Ras transformation of RIE-1 epithelial cells. Proc. Natl. Acad. Sci. U.S.A., 93:6924-6928 (1996).
161. Ollivier, V., G. C. N. Parry, R. R. Cobb, D. DeProst, and N. Mackman: Elevated cyclic AMP inhibits NfκB-mediated transcription in human monocytic cells and endothelial cells. J. Biol. Chem., 271:20828-20835 (1996).
162. Orphanides, G., T. Lagrange, and D. Reinberg: The general transcription factors of RNA polymerase II. Genes Dev., 10:2657-2683 (1996).
163. Pankov, R., A. Umezawa, R. Maki, C. J. Der, C. A. Hauser, and R. G. Oshima: Oncogene activation of human keratin 18 transcription via the Ras signal transduction pathway. Proc. Natl. Acad. Sci. U.S.A., 91:873-877 (1994).
164. Park, S.-H. and R. A. Weinberg: A putative effector of Ral has homology to Rho/Rac GTPase activating proteins. Oncogene, 11:2349-2355 (1995).
165. Parker, D., K. Ferreri, T. Nakajima, V. J. LaMorte, R. Evans, S. C. Koerber, C. Hoeger, and M. R. Montminy: Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism. Mol. Cell. Biol., 16:694-703 (1996).
166. Pawson, T.: Protein modules and signaling networks. Nature, 373:573-580 (1995).
167. 2+ influx. J. Biol. Chem., 271:7883-7886 (1996).
168. Perona, R., S. Montaner, L. Saniger, I. Sanchez-Perez, R. Bravo, and J. C. Lacal: Activation of the nuclear factor-κB by Rho, Cdc42 and Rac-1 proteins. Genes Dev., 11:463-475 (1997).
169. Plattner, R., M. J. Anderson, K. Y. Sato, C. L. Fasching, C. J. Der, and E. J. Stanbridge: Loss of oncogenic ras expression does not correlate with loss of tumorigenicity in human cells. Proc. Natl. Acad. Sci. U.S.A., 93:6665-6670 (1996).
170. Pombo, C. M., J. V. Bonventre, J. Avruch, J. R. Woodgett, J. M. Kyriakis, and T. Force: The stress-activated protein kinases are major c-Jun amino-terminal kinases activated by ischemia and reperfusion. J. Biol. Chem., 269:26546-26551 (1994).
171. Ponting, C. P. and D. R. Benjamin: A novel family of Rasbinding domains. Trends Biochem. Sci., 21:422-425.
172. Post G. R. and J. H. Brown: G protein-coupled receptors and signaling pathways regulating growth responses. FASEB J., 10:741-749 (1996).
173. Powell, C. T., J. E. Gschwend, W. R. Fair, N. J. Brittis, D. Stec, and R. Huryk: Overexpression of protein kinase C-ζ inhibits invasive and metastatic abilities of Dunning R-3327 MAT-LyLu rat prostate cancer cells. Cancer Res., 56
174. Price, M. A., F. H. Cruzalegui, and R. Treisman: The p38 and ERK MAP kinase pathways cooperate to activate ternary complex factors and c-fos transciption in response to UV light. EMBO J., 15:6552-6563 (1996).
175. Phox are targets for Cdc42Hs and Rac1 in neutrophils. J. Biol. Chem., 270:10717-10722 (1995).
176. Qiu, R.-G., J. Chen, D. Kirn, F. McCormick, and M. Symons: An essential role for Rac in Ras transformation. Nature, 374:457-459 (1995a).
177. Qiu, R.-G., J. Chen, F. McCormick, and M. Symons: A role for Rho in Ras transformation. Proc. Natl. Acad. Sci. U.S.A., 92:11781-11785 (1995b).
178. Quilliam, L. A., R. Khosravi-Far, S. Y. Huff, and C. J. Der: Guanine nucleotide exchange factors: activators of the Ras superfamily of proteins. BioEssays, 17:395-404 (1995).
179. Rana, A., K. Gallo, P. Godowski, S.-I. Hirai, S. Ohno, L. Zon, J. M. Kyriakis, and J. Avruch: The mixed lineage kinase SPRK phosphorylates and activates the stressactivated protein kinase activator, SEK-1. J. Biol. Chem., 271:19025-19028 (1996).
180. Reddy, M. A., S. J. Langer, M. S. Colman, and M.C. Ostrowski: An enhancer element responsive to ras and fms signaling pathways is composed of two distinct nuclear factor binding sites. Mol. Endocrinol. 6:1051-1060 (1992).
181. Ren, X.-D., G. M. Bokoch, A. Traynor-Kaplan, G. H. Jenkins, R. A. Anderson, and M. A. Schwarte: Physical association of the small GTPase Rho with a 68-kDa phosphatidylinositol 4-phosphate 5-kinase in Swiss 3T3 cells. Mol. Biol. Cell, 7:435-442 (1996).
182. Rodriguez-Viciana, P., P. H. Warne, A. Khwaja, B. M. Matte, D. Pappin, P. Das, M. D. Waterfield, A. Ridley, and J. Downward: Role of phosphoinositi.de 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras. Cell, 89:457-467 (1997).
183. Roeder, R. G.: The role of general initiation factors in transcription by RNA polymerase H. Trends Biochem. Sci., 21:327-335 (1996).
184. Rollo, E. E., D. L. Laskin, and D. T. Denhardt: Osteopontin inhibits nitric oxide production and cytotoxicity by activated RAW264.7 macrophages. J. Leukocyte Biol., 60:397-404 (1996),
185. Roy, A. L., C. Carruthers, T. Gutjahr and R. G. Roeder: Direct role for Myc in transcription initiation mediated by interactions with TFII-I. Nature, 365:359-361 (1993).
186. Roy, B., J. Beamon, E. Balint, and D. Reisman: Transactivation of the human p53 tumor suppressor gene by c-Myc/Max contributes to elevated mutant p53 expression in some tumors. Mol. Cell. Biol., 14:7805-7815 (1994).
187. Saez, E., S. E. Rutberg, E. Mueller, H. Oppenheim, J. Smoluk, S. H. Yuspa, and B. M. Spiegelman: C-fos is required for malignant progression of skin tumors. Cell, 82:721-732 (1995).
188. 1-adrenergic receptor signaling in cardiomyocytes. J. Biol. Chem., 271:31185-31190 (1996).
189. Scherer, D. C., J. A. Brockman, Z. Chen, T. Maniatis, and D. W. Ballard: Signal-induced degradation of IκBα requires site-specific ubiquitination. Proc. Natl. Acad. Sci. U.S.A., 92:11259-11263 (1995).
190. 2 of p65 NfκB. J. Biol. Chem., 270:15576-15584 (1995).
191. Schwartz, M. A., D. Toksoz, and R. Khosravi-Far: Transformation by Rho exchange factor oncogene is mediated by activation of an integrin-dependent pathway. EMBO J., 15:6525-6530 (1996).
192. Schwarz, E. M., D. van Antwerp, and I. M. Verma: Constitutive phosphorylation of IκBα by casein kinase II occurs preferentially at serine 293: requirement for degradation of free IκBα. Mol. Cell. Biol., 16:3554-3559 (1996).
193. Seger, R. and E. G. Krebs: The MAPK signaling cascade. FASEB J., 9:726-735 (1995).
194. Seth, A., F. A. Gonzalez, S. Gupta, D. L. Raden, and R. J. Davis: Signal transduction within the nucleus by mitogen-activated protein kinase. J. Biol. Chem., 267:24796-24804 (1992).
195. Sgouras, D. N., M. A. Athanasiou, G. J. Beal, Jr., R. J. Fisher, D. G. Blair, and G. J. Mavrothalassitis: ERF: an ETS domain protein with strong transcriptional represser activity, can suppress ets-associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation. EMBO J., 14:4781-4793 (1995).
196. Shuman, J. D., J. Cheong, and J. E. Coligan: ATF-2 and C/ EBPa can form a heterodimeric DNA binding complex in vitro. J. Biol. Chem., 272:12793-12800 (1997).
197. Siebenlist, U., G. Franzoso, and K. Brown: Structure, regulation and function of NF-κB. Annu. Rev. Cell Biol., 10:405-55 (1994).
198. Silberman, S., M. Janulis, and R. M. Shultz: Characterization of downstream Ras signals that induce alternative protease-dependent invasive phenotypes. J. Biol. Chem., 272:5927-5935 (1997).
199. Singh, S., B. G. Darnay, and B. B. Aggarwal: Site-specific tyrosine phosphorylation of IκBα negatively regulates its inducible phosphorylation and degradation. J. Biol. Chem., 271:31049-31054 (1966).
200. Spaargaren, M. and J. R. Bischoff: Identification of the guanine nucleotide dissociation stimulator for Ral as a putative effector molecule of R-ras, H-ras, and Rap. Proc. Natl Acad. Sci. U.S.A., 91:12609-12613 (1994).
201. Sulciner, D. J., K. Irani, Z.-X. Yu, V. J. Ferrans, P. Goldschmidt-Clermont, and T. Finkel: rac1 regulates a cytokine-stimulated redox-dependent pathway necessary for NFκB activation. Mol. Cell. Biol., 16:7115-7121 (1996).
202. Sun, S.-C., J. Elwood, and W. C. Greene: Both amino- and carboxyl-terminal sequences within IκBα regulate its inducible degradation. Mol. Cell. Biol., 16:1058-1065 (1996).
203. Swope, D. L., C. L. Mueller, and J. C. Chrivia: CREB-binding protein activates transcription through multiple domains. J. Biol. Chem., 271:28138-28145 (1996).
204. Symons, M.: Rho family GTPases: the cytoskeleton and beyond. Trends Biochem. Sci., 21:178-181 (1996).
205. Symons, M., J. M. J. Derry, B. Kariak, S. Jiang, V. Lemahieu, F. McCormick, W. Francke, and A. Abo: Wiskott-Aldrich syndrome protein, a novel effector for the GTPase Cdc42Hs, is implicated in actin polymerization. Science, 84:723-734 (1996).
206. Takai, Y., T. Sasaki, K. Tanaka, and H. Nakanishi: Rho as a regulator of the cytoskeleton. Trends Biochem. Sci., 20:227-231 (1995).
207. Thanos, D. and T. Maniatis: NF-KB: a lesson in family values. Cell, 80:529-532 (1995).
208. Tibbles, L. A., Y. L. Ing, F. Kiefer, J. Chan, N. Iscove, J. R. Woodgett, and N. J. Lassam: MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/ 6. EMBO J., 15:7026-7035 (1996).
209. Treisman, R.: Regulation of transcription by MAP kinase cascades. Curr. Opin. Cell Biol., 8:205-215 (1996).
210. Twamley-Stein, G., E. Kowenz-Leutz, S. Ansieau, and A. Leutz: Regulation of C/EBPβ/NF-M activity by kinase oncogenes. Curr. Topics Micro. Immunol., 211:129-136 (1996).
211. Ubeda, M., X.-Z. Wang, H. Zinszner, I. Wu., J. F. Habener, and D. Ron: Stress-induced binding of the transcription factor CHOP to a novel DNA control element. Mol. Cell. Biol., 16:1479-1489 (1996).
212. Ueda, Y., S.-I. Hirai, S.-I. Osada, A. Suzuki, K. Mizuno, and S. Ohno: Protein kinase Cδ activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf. J. Biol Chem., 271:23512-23519 (1996).
213. van Biesen, T., B. E. Hawes, D. K. Luttrell, K. M. Krueger, K. Touhara, E. Rorfiri, M. Sakaue, L. M. Luttrell, and R. J. Lefkokowitz: Receptor-tyrosine-kinase- and Gβγ-mediated MAP kinase activation by a common signaling pathway. Nature, 376:781-784 (1995).
214. van Dam, H., D. Wilhelm, I. Herr, A. Steffen, P. Herrlich, and P. Angel: ATF2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents. EMBO J., 14:1798-1811 (1995).
215. Vandel, L., N. Montreau, E. Vial, C. M. Pfarr, B. Binetruy, and M. Castellanzzi: Stepwise transformation of rat embryo fibroblasts: c-Jun, JunB, or JunD can cooperate with Ras for focus formation, but a c-Jun-containing heterodimer is required for immortalization. Mol. Cell. Biol., 16:1881-1888 (1996).
216. van der Geer, P., T. Hunter, and R. A. Lindberg: Receptor protein-tyrosine kinases and their signal transduction pathways. Annu. Rev. Cell. Biol., 10:51-337 (1994).
217. van der Greer, P., M. Henkemeyer, T. Jacks, and T. Pawson: Aberrant Ras regulation and reduced p190 tyrosine phosphorylation in cells lacking p120-GAP. Mol. Cell. Biol., 17:1840-1847 (1997).
218. van Leeuwen, F. N., R. A. van der Kammen, G. G. Habets, and J. G. Collard: Oncogenic activity of Tiam1 and Rac1 in NIH3T3 cells. Oncogene, 11:2215-2221 (1995).
219. Verrijzer, C. P. and R. Tjian: TAFs mediate transcriptional activation and promoter selectivity. Trends Biochem. Sci., 21:338-342 (1996).
220. Vincent, S. and J. Settleman: The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol. Cell. Biol., 17:2247-2256 (1997).
221. Vojtek, A. B. and J. A. Cooper: Rho family members: activators of MAP kinase cascades. Cell, 82:527-529 (1995).
222. Wagner, A. C. and J. A. Williams: Low molecular weight GTP-binding proteins: molecular switches regulating diverse cellular functions. Am. J. Physiol., 266: G1-14 (1994).
223. Wang, X. and D. Ron: Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP kinase. Science, 272:1347-1349 (1996).
224. Wartmann, M., P. Hofer, P. Turowski, A. R. Saltiel, and N. E. Hynes: Negative modulation of membrane localization of the Raf-1 protein tinase by hyperphosphorylation. J. Biol. Chem., 272:3915-3923 (1997).
225. Wasylyk, B., C. Wasylyk, P. Flores, A. Begue, D. Leprince, and D. Stehelin: The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation. Nature, 346:191-193 (1990).
226. Watanabe, G., Y. Saito, P. Madaule, T. Ishizaki, K. Fujisawa, N. Morii, H. Mukai, Y. Ono, A. Kakizuka, and S. Narumiya: Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho. Science, 271:645-648 (1996).
227. Wesselborg, S., M. K. A. Bauer, M. Vogt, M. L. Schmitz, and K. Schulze-Osthoff: Activation of transcription factor NFκB and p38 MAPK is mediated by distinct and separate stress effector pathways. J. Biol. Chem., 272:12422-12429 (1997).
228. White, M. A., T. Vale, J. H. Camonis, E. Schaefer, and M. H. Wigler: A role for the Ral guanine nucleotide dissociation stimulator in mediating Ras-induced transformation. J. Biol. Chem., 271:16439-16442 (1996).
229. Whitmarsh, A. J., S.-H. Yang, M. S.-S. Su, A. D. Sharrocks, and R. J. Davis: Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors. Mol. Cell. Biol., 17:2360-2371 (1997).
230. Wiesmuller, L. and F. Wittinghofer: Signal transduction pathways involving ras. Cell. Signaling, 6:247-267 (1994).
231. Wittinghofer, A. and N. Nassar: How Ras-related proteins talk to their effectors. Trends Biochem. Sci., 21:488-491 (1996).
232. Wu, H., K. Moulton, A. Horval, S. Parik, and C. K. Glass: Combinatorial interactions between Ap-1 and ets domain proteins contribute to the developmental regulation of the macrophage scavenger receptor gene. Mol. Cell Biol., 14:2129-2139 (1994).
233. Xing, J., D. D. Ginty, and M. E. Greenberg: Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science, 273:959-963 (1996).
234. Xu, S., D. Robbins, J. Frost, A. Dang, C. Lange-Carter, and M. H. Cobb: MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of mitogen-activated protein kinase. Proc. Natl. Acad. Sci. U.S.A., 92:6808-6812 (1995).
235. Yang, B.-S., C. A. Hauser, G. Henkel., M. S. Colman, C. van Beveren, K. J. Stacey, D. A. Hume, R. A. Maki, and M. C. Ostrowski: Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets-1 andc-Ets2. Mol. Cell. Biol., 16:538-547 (1996).
236. Zervos, A. S., L. Faccio, J. P. Gatto, J. M. Kyriakis, and R. Brent: Mxi2, a mitogen-activated protein kinase that recognizes and phosphorylates Max protein. Proc. Natl. Acad. Sci. U.S.A., 92:10531-10534 (1995).
237. Zhang, S., J. Han, M. A. Sells, J. Chernoff, U. G. Knaus, R. J. Ulevitch, and G. M. Bokoch: Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J. Biol Chem., 270:23934-23936 (1995).
238. Zhou, M-M., K. S. Ravichandran, E. T. Olejniczak, A. M. Petros, R. P. Meadows, M. Sattler, J. E. Harlan, W. S. Wade, S. J. Burakoff, and S. W. Fesik: Structure and ligand recognition of the phosphotyrosine binding domain of She. Nature, 378:584-592.