G protein-coupled receptors and signaling pathways regulating growth responses

FASEB Journal

Volumn 10, Issue 7, 1996, Pages 741-749

  Post, Ginell R ^a   Brown, Joan Heller ^a  

^a San Diego   (United States)

Author keywords

c Jun NH2 terminal kinases; gene expression; hypertrophy; mitogen activated protein kinases; mitogenesis; Ras effectors; transformation; tyrosine phosphorylation

Indexed keywords

CYCLIC AMP DEPENDENT PROTEIN KINASE; GROWTH FACTOR RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; MEMBRANE RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; PERTUSSIS TOXIN; PROTEIN KINASE C; PROTEIN TYROSINE KINASE;

CELL GROWTH; CELL TYPE; ENZYME ACTIVITY; GENE EXPRESSION; GROWTH REGULATION; HUMAN; MITOGENESIS; ONCOGENE C JUN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

EID: 0029900434     PISSN: 08926638     EISSN: None     Source Type: Journal    
DOI: 10.1096/fasebj.10.7.8635691     Document Type: Review

References (137)

1. LaMorte, V. J., Harootunian, A. T., Spiegel, A. M., Tsien, R. Y., and Feramisco, J. R. (1993) Mediation of growth factor induced DNA synthesis and calcium mobilization by Cq and Gi2. J. Cell Biol. 121, 91-99
2. Baffy, G., Yang, L., Raj, S., Manning, D. R., and Williamson, J. R. (1994) G protein coupling to the thrombin receptor in Chinese hamster lung fibroblasts. J. Biol. Chem. 269, 8483-8487
3. Meinkoth, J. L., Goldsmith, P. K. Spiegel, A. M., Feramisco, J. R., and Burrow, G. N. (1992) Inhibition of thyrotropin-induced DNA synthesis in thyroid follicular cells by microinjection of an antibody to the stimulatory G protein of adenylate cyclase, Gs. J. Biol. Chem. 267, 13239-13245
4. Aragay, A. M., Collins, L. R., Post, G. R., Watson, A. J., Feramisco, J. R., Brown, J. H., and Simon, M. I. (1995) G12 requirement for thrombin-stimulated gene expression and DNA synthesis in 1321N1 astrocytoma cells. J. Biol. Chem. 270, 20073-20077
5. 11]substance P. J. Biol. Chem. 270, 8623-8628
6. Lamy, F., Wilkin, F., Baptist, M., Posada, J., Roger, P. P., and Dumont, J. E. (1993) Phosphorylation of mitogen-activated protein kinase is involved in the epidermal growth factor and phorbol ester, but not in the thyrotropin/cAMP, thyroid mitogenic pathway. J. Biol. Chem. 268, 8398-8401
7. Post, G. R., Goldstein, D., Thuerauf, D., Glembotski, C., C., and Brown, J. H. (1996) Dissociation of p44 and p42 mitogen-activated protein kinase activation from receptor induced hypertrophy in neonatal rat ventricular myocytes. J. Biol. Chem. 271, 8452-8457
8. Gallego, C., Gupta, S. K., Heasley, L. E., Qian, N., and Johnson, G. L. (1992) Mitogen-activated protein kinase activation resulting from selective oncogenic expression in NIH 3T3 and Rat 1a cells. Proc. Natl. Acad. Sci. USA 89, 7355-7359
9. Meloche, S., Seuwen, K., Pages, G., and Pouyssegur, J. (1992) Biphasic and synergistic activation of p44 mapk (ERK1) by growth factors: Correlation between late phase activation and mitogenicity. Mol. Endocrinol. 6, 845-854
10. Seuwen, K., Magnaldo, I., and Pouyssegur, J. (1988) Serotonin stimulates DNA synthesis in fibroblasts acting through 5-HT1B receptors coupled to a Gi-protein. Nature (London) 335, 254-256
11. Julius, D., Livelli, T. J., Jessell, T. M., and Axel, R. (1989) Ectopic expression of the serotonin lc receptor and the triggering of malignant transformation. Science 244, 1057-1062
12. Vicentini, L. M., and Villereal, M. L. (1984) Serum, bradykinin and vasopressin stimulate release of inositol phosphates from human fibroblasts. Biochem. Biophys. Res. Cummun. 123, 663-670
13. Nilsson, J., von Euler, A. M., and Dalsgaard, C. (1985) Stimulation of connective tissue cell growth by substance P and substance K. Nature (London) 315, 61-63
14. Jackson, T.R., Blair, L.A.C., Marshall, J., Goedert, M., and Hanley, M. R. (1988) The mas oncogene encodes an angiotensin receptor. Nature (London) 335, 437-440
15. Asuda, J., Richmond, K. M., and Otto, A. M. (1981) Two growth factors and two hormones regulate initiation of DNA synthesis in cultured mouse cells through different pathways of events. Proc. Natl. Acad. Sci. USA 78, 1004-1008
16. Stephens, E. V., Kalinec, G., Brann, M. R., and Gutkind, J. S. (1993) Transforming G protein-coupled receptors transduce potent mitogenic signals in NIH 3T3 cells independent of cAMP inhibition or conventional protein kinase C. Oncogene 8, 19-26
17. Ashkenazi, A., Ramachandran, J., and Capon, D. J. (1989) Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes. Nature (London) 340, 146-150
18. Gutkind, J. S., Novotny, E. A., Brann, M. R., and Robbins, K. C. (1991) Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes. Proc. Natl. Acad. Sci. USA 88, 4703-4707
19. 1 muscarinic receptors heterologously expressed in cardiac myocytes mediate Ras-dependent changes in gene expression. J. Biol. Chem. 270, 8446-8451
20. Greene, L. A., and Tischler, A. S. (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc. Natl. Acad. Sci. USA 73, 2424-2428
21. Pinkas-Kramarski, R., Stein, R., Lindenboim, L., and Sokolovsky, M. (1992) Growth factor-like effects mediated by muscarinic receptors in PG12M1 cells. J. Neurochem. 59, 2158-2166
22. Whitman, M., and Cantley, L. (1988) Phosphoinositide metabolism and the control of cell proliferation. Biochim. Biophys. Acta 948, 327-344
23. Hug, H., and Sarre, T. F. (1993) Protein kinase C isoenzymes: Divergence in signal transduction? Biochem. J. 291, 329-343
24. Nishizuka, Y. (1992) Intracellular signaling by hydrolysis of phospholipids and activitation of protein kinase C. Science 258, 607-614
25. van Corven, E. J., Groenink, A., Jalink, K., Eichholtz, T., and Moolenaar, W. H. (1989) Lysophosphatidate-induced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins. Cell 59, 45-54
26. Seuwen, K., Kahan, C., Hartmann, T., and Pouyssegur, J. (1990) Strong and persistent activation of inositol lipid breakdown induces early mitogenic events but not Go to S phase progression in hamster fibroblasts. J. Biol. Chem. 265, 22292-22299
27. q-alpha potentiates platelet-derived growth factor-stimulated mitogenesis in confluent cell cultures. J. Biol. Chem. 269, 19671-19674
28. Cazaubon, S.M., Ramos-Morales, F., Fischer, S., Schweighoffer, F., Strosberg, A.D., and Couraud, P. (1994) Endothelin induces tyrosine phosphorylation and GRB2 association of Shc in astrocytes. J. Biol. Chem. 269, 24805-24809
29. De Vivo, M., Chen, J., Codina, J., and Iyengar, R. (1992) Enhanced phospholipase C stimulation and transformation in NIH-3T3 cells expressing Q209LGq-α-subunits. J. Biol. Chem. 267, 18263-18266
30. 1B-adrenergic receptor enhances mitogenesis and tumorigenesis. Proc. Natl. Acad. Sci. USA 88, 11354-11358
31. Kalinec, G., Nazarali, A. J., Hermouet, S., Xu, N., and Gutkind, J.S. (1992) Mutated α subunit of the Gq protein induces malignant transformation in NIH 3T3 cells. Mol. Cell. Biol. 12, 4687-4693
32. Nemecek, G. M., Coughlin, S. R., Handley, D. A., and Moskowitz, M. A. (1986) Stimulation of aortic smooth muscle cell mitogeneses by serotinin. Proc. Natl. Acad. Sci. USA 83, 674-678
33. Chambard, J.C., Paris, S., L'Allemain, G., and Pouyssegur, J. (1987) Two growth factor signalling pathways in fibroblasts distinguished by pertussis toxin. Nature (London) 326, 800-803
34. Rozengurt, E., and Sinnett-Smith, J. (1983) Bombesin stimulation of DNA synthesis in cultures of Swiss 3T3 cells. Proc. Natl. Acad. Sci. USA 80, 2936-2940
35. Letterio, J. L., Coughlin, S. R., and Williams, L. T. (1986) Pertussis toxin-sensitive pathway in the stimulation of c-myc expression and DNA synthesis by bombesin. Science 234, 1117-1119
36. Murayama, T., and Ui, M. (1987) Possible involvement of a GTP-binding protein, the substrate of islet activating protein, in receptor-mediated signaling responsible for cell proliferation. J. Biol. Chem. 262, 12463-12467
37. i2 induces neoplastic transformation of Rat-1 cells. Proc. Natl. Acad. Sci. USA 88, 7031-7035
38. Gupta, S. K., Gallego, C., Lowndes, J. M., Pleiman, C. M., Sable, C., Eisfelder, B. J., and Johnson, G. L. (1992) Analysis of the fibroblast transformation potential of GTPase-deficient gip2 oncogenes. Mol. Cell. Biol. 12, 190-197
39. 2 protein have opposite effects on proliferation of NIH 3T3 cells. Proc. Natl. Acad. Sci. USA 88, 10455-10459
40. Spiegel, A. M., Shenker, A., and Weinstein, L. S. (1992) Receptor-effector coupling by G proteins: Implications for normal and abnormal signal transduction. Endocrine Rev. 13, 536-565
41. Rozengurt, E. (1986) Early signals in the mitogenic response. Science 234, 161-166
42. Spada, A., Vallar, L., and Faglia, G. (1993) G-proteins and hormonal signalling in human pituitary tumors: Genetic mutations and functional alterations. Frontiers Neuroendocrinol. 14, 214-232
43. Dumont, J. E., Jauniaux, J.-C., and Roger, P. P. (1989) The cyclic AMP-mediated stimulation of cell proliferation. Trends Biochem. Sci. 14, 67-71
44. Huang, N., Wang, D., Gonzalez, F., and Heppel, L. A. (1991) Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells: II. A pathway involving arachidonic acid release, prostaglandin synthesis, and cyclic AMP production. J. Cell. Physiol. 146, 483-494
45. Papavassiliou, A. G. (1994) The CREB/ATF family of transcription factors: Modulation by reverse phosphorylation. Anticancer Res. 14, 1801-1805
46. Meyer, T. E., and Habener, J. F. (1993) Cyclic adenosine 3′, 5′-monophosphate response element binding protein (CREB) and related transcription-activating deoxyribonucleic acid-binding proteins. Endocrine Rev. 14, 269-290
47. Borrelli, E., Montmayeur, J. P., Foulkes, N. S., and Sassone-Corsi, P. (1992) Signal transduction and gene control: The cAMP pathway. Crit. Rev. Oncogenesis 3, 321-338
48. Cook, S. J., and McCormick, F. (1993) Inhibition by cAMP of Ras-dependent activation of Raf. Science 262, 1069-1072
49. Jalink, K., Hordijk, P. L., and Moolenaar, W. H. (1994) Growth factor-like effects of lysophosphatidic acid, a novel lipid mediator. Biochim. Biophys. Acta 1198, 185-196
50. 13 subunits define a fourth class of G protein α subunits. Proc. Natl. Acad. Sci. USA 88, 5582-5586
51. 12 gene product. Mol. Cell. Biol. 13, 762-768
52. 12 potentiates the eicosanoid pathway and is highly oncogenic in NIH 3T3 cells. Proc. Natl. Acad. Sci. USA 90, 6741-6745
53. 12. FEBS Lett. 330, 319-322
54. 13 proteins induce neoplastic transformation of Rat-1 fibroblasts. Oncogene 9, 2559-2565
55. 13 induces Egr-1, c-fos, and transformation in NIH 3T3 cells. Oncogene 9, 2425-2429
56. 2 and thrombin receptors in human platelets. Proc. Natl. Acad. Sci. USA 91, 504-508
57. 13 stimulates Na-H exchange. J. Biol. Chem. 269, 4721-4724
58. 12 class of G proteins. J. Biol. Chem. 269, 11802-11806
59. 13. J. Biol. Chem. 270, 18655-18659
60. Mulcahy, L. S., Smith, M. R., and Stacey, D. W. (1985) Requirement for Ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells. Nature (London) 313, 241-243
61. Szeberenyi, J., Cai, H., and Cooper, G. M. (1993) Effect of a dominant inhibitory Ha-Ras mutation on neuronal differentiation of PC12 cells. Mol. Cell. Biol. 10, 5324-5332
62. Leevers, S. J., Paterson, H. F., and Marshall, C. J. (1994) Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature (London) 369, 411-414
63. Hunter, T., and Karin, M. (1992) The regulation of transcription by phosphorylation. Cell 70, 375-387
64. LaMorte, V. J., Kennedy, E. D., Collins, L. R., Goldstein, D., Harootunian, A. T., Brown, J. H., and Feramisco, J. R. (1993) A requirement for Ras protein function in thrombin-stimulated mitogenesis in astrocytoma cells. J. Biol. Chem. 268, 19411-19415
65. Kupperman, E., Wen, W., and Meinkoth, J. L. (1993) Inhibition of thyrotropin-stimulaled DNA synthesis by microinjenction of inhibitors of cellular Ras and cyclic AMP-dependent protein kinase. Mol. Cell. Biol. 13, 4477-4484
66. Cook, S. J., Rubinfeld, B., Albert, I., and McCormick, F. (1993) RAPV12 antagonizes Ras-dependent activation of ERK1 and ERK2 by LPA and EGF in Rat-1 fibroblasts. EMBOJ. 12, 3475-3485
67. van Corven, E. J., Hordijk, P. L., Medema, R. H., Bos, J. L., and Moolenaar, W. H. (1993) Pertussis toxin-sensitive activation of p21ras by G protein-coupled receptor agonists in fibroblasts. Proc. Natl. Acad. Sci. USA 90, 1257-1261
68. Winitz, S., Russell, M., Qian, N., Gardner, A., Dwyer, L., and Johnson, G. L. (1993) Involvement of Ras and Raf in the Gi-coupled acetylcholine muscarinic m2 receptor activation of mitogen-activated protein (MAP) kinase kinase and MAP kinase. J. Biol. Chem. 268, 19196-19199
69. 2-adrenergic receptors expressed in fibroblasts. J. Biol. Chem. 268, 22235-22238
70. Thorburn, J., and Thorburn, A. (1994) The tyrosine kinase inhibitor, genestein, prevents α-adrenergic-induced cardiac muscle cell hypertrophy by inhibiting activation of the Ras-MAP kinase signaling pathway. Biochem. Biophys. Res. Commun. 202, 1586-1591
71. Chen, Y.-H., Pouyssegur, J., Courtneidge, S. A., and Van Obberghen-Schilling, E. (1994) Activation of Src family kinase activity by the G protein-coupled thrombin receptor in growth-responsive fibroblasls. J. Biol. Chem. 269, 27372-27377
72. Faure, M., Voyno-Yasenetskaya, T. A., and Bourne, H. R. (1994) cAMP and βγ subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. J. Biol. Chem. 269, 7851-7854
73. Crespo, P., Xu, N., Simonds, W. F., and Gutkind, J. S. (1994) Ras-dependent activation of MAP kinase pathway mediated by C-protein βγ subunits. Nature (London) 369, 418-420
74. ras. Proc. Natl. Acad. Sci. USA 91, 12706-12710
75. Hawes, B. E., van Biesen, T., Koch, W. J., Luttrell, L. M., and Lefkowitz, R. J. (1995) Distinct pathways of Gi- and Gq-mediated mitogen-activated protein kinase activation. J. Biol. Chem. 270, 17148-17153
76. Touhara, K., Inglese, J., Pitcher, J. A., Shaw, G., and Lefkowitz, R. J. (1994) Binding of G protein βγ-subunits to pleckstrin homology domains. J. Biol. Chem. 269, 10217-10220
77. van Biesen, T., Hawes, B. E., Luttrell, D. K., Krueger, K. M., Touhara, K., Porfiri, E., Sakaue, M., Luttrell, L. M., and Lefkowitz, R. J. (1995) Receptor-tyrosine-kinase- and Gβγ-mediated MAP kinase activation by a common signalling pathway. Nature (London) 376, 781-784
78. Pelech, S. L., and Sanghera, J. S. (1992) MAP kinases: Charting the regulatory pathways. Science 257, 1355-1356
79. Chen, R., Sarnecki, C., and Blenis, J. (1992) Nuclear localization and regulation of erk- and rsk-encoded protein kinases. Mol. Cell. Biol. 12, 915-927
80. Lenormand, P., Sardet, C., Pages, G., L'Allemain, G., Brunet, A., and Pouyssegur, J. (1993) Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase (p45mapkk) in fibroblasts. J. Cell Biol. 122, 1079-1088
81. Davis, R. J. (1993) The mitogen-activated protein kinase signal transduction pathway. J. Biol. Chem. 268, 14553-14556
82. Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M.J., Waterfield, M.D., and Downward, J. (1994) Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature (London) 370, 527-532
83. Kahan, C., Seuwen, K., Meloche, S., and Pouyssegur, J. (1992) Coordinate, biphasic activation of p44 mitogen-activated protein kinase and S6 kinase by growth factors in hamster fibroblasts. Evidence for thrombin-induced signals different from phosphoinositide turnover and adenylylcyclase inhibition. J. Biol. Chem. 267, 13369-13375
84. ras activity and consequent prolonged ERK activity. Neuron 9, 705-717
85. Cowley, S., Paterson, H., Kemp, P., and Marshall, C. J. (1994) Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 77, 841-852
86. mapk are required for fibroblast proliferation. Proc. Natl. Acad. Sci. USA 90, 8319-8323
87. Pang, L., Sawada, T., Decker, S. J., and Saltiel, A. R. (1995) Inhibition of MAP kinase kinase blocks the differentiation of PC-12 cells induced by nerve growth factor. J. Biol. Chem. 270, 13585-13588
88. raf-1. J. Biol. Chem. 268, 20717-20720
89. Honda, Z., Takano, T., Gotoh, Y., Nishida, E., Ito, K., and Shimizu, T. (1994) Transfected platelet-activating factor receptor activates mitogen-activated protein (MAP) kinase and MAP kinase kinase in Chinese hamster ovary cells. J. Biol. Chem. 269, 2307-2315
90. Pumiglia, K. M., LeVine, H., Haske, T., Habib, T., Jove, R., and Decker, S. J. (1995) A direct interaction between G-protein βγ subunits and the Raf-1 protein kinase. J. Biol. Chem. 270, 14251-14254
91. Kolch, W., Heldecker, G., Kochs, G., Hummel, R., Vahidi, H., Mischak, H., Finkenzeller, G., Marme, D., and Rapp, U. (1993) Protein kinase Cα activates RAF-1 by direct phosphorylation. Nature (London) 364, 249-252
92. Thorburn, J., Frost, J. A., and Thorburn, A. (1994) Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy. J. Cell Biol. 126, 1565-1572
93. Al-Alawi, N., Rose, D. W., Buckmaster, C., Ahn, N., Rapp, U., Meinkoth, J., and Feramisco, J. R. (1995) Thyrotropin-induced mitogenesisis Ras dependent but appears to bypass the Raf-dependent cytoplasmic kinase cascade. Mol. Cell. Biol. 15, 1162-1168
94. ras proteins and their GTPase activating proteins. Cancer Surveys 12, 25-42
95. Kikuchi, A., Demo, S. D., Ye, Z., Chen, Y., and Williams, L. T. (1994) ralGDS family members interact with the effector loop of ras p21. Mol. Cell. Biol. 14, 7438-7491
96. Sjolander, A., Yamamoto, K., Huer, B. E., and Lapetina, E. G. (1991) Association of p21ras with phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. USA 88, 7908-7912
97. Qiu, R., Chen, J., Kirn, D., McCormick, F., and Symons, M. (1995) An essential role for Rac in Ras transformation. Nature (London) 374, 457-459
98. Aullo, P., Giry, M., Olsnes, S., Popoff, M.R., Kocks, C., and Boquet, P. (1993) A chimeric toxin to study the role of the 21 kDa GTP binding protein Rho in the control of actin microfilament assembly. EMBO J. 12, 921-931
99. Yamamoto, M., Marui, N., Sakai, T., Mori, N., Kozaki, S., Ikai, K., Imamura, S., and Narumiya, S. (1993) ADP-ribosylation of the RhoA gene product by botulinum C3 exotoxin causes Swiss 3T3 cells to accumulate in the G1 phase of the cell cycle. Oncogene 8, 1449-1455
100. Jalink, K., van Corven, E.J., Hengeveld, T., Morii, N., Narumiya, S., and Moolenaar, W. H. (1994) Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho. J. Cell Biol. 126, 801-810
101. Hill, C. S., Wynne, J., and Treisman, R. (1995) The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF. Cell 81, 1159-1170
102. Ridley, A. J., and Hall, A. (1992) The small CTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70, 389-399
103. Nobes, C. D., and Hall, A. (1995) Rho, rac and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53-62
104. Kozina, R., Ahmed, S., Best, A., and Lim, L. (1995) The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol. Cell. Biol. 15, 1942-1952
105. Ridley, A. J., Paterson, H. F., Johnston, C.L., Diekmann, D., and Hall, A. (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70, 401-410
106. Lange-Carter, C. A., Pleiman, C. M., Gardner, A. M., Blumer, K. J., and Johnson, G. L. (1993) A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science 260, 315-319
107. Derijard, B., Hibi, M., Wu, I., Barrett, T., Su, B., Deng, T., Karin, M., and Davis, R. J. (1994) JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76, 1025-1037
108. Lin, A., Minden, A., Martinetto, H., Claret, F.-X., Lange-Carter, C., Mercurio, F., Johnson, G. L., and Karin, M. (1995) Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science 268, 286-290
109. Coso, O. A., Chiariello, M., Yu, J. C., Teramoto, H., Crespo, P., Xu, N., Miki, T., and Gutkind, J. S. (1995) The small GTP binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 81, 1137-1146
110. Minden, A., Lin, A., Claret, F.-X., Abo, A., and Karin, M. (1995) Selective activation of the JNK Signaling cascade and c-Jun transcriptional activity by the Small GTPases Rac and Cdc42. Cell 81, 1147-1157
111. Whitmarsh, A. J., Shore, P., Sharrocks, A. D., and Davis, R. J. (1995) Integration of MAP kinase signal transduction pathways at the serum response element. Science 269, 403-407
112. Marais, R., Wynne, J., and Treisman, R. (1993) The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell 73, 381-393
113. Minden, A., Lin, A., Smeal, T., Derijard, B., Cobb, M., Davis, R., and Karin, M. (1994) c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases. Mol. Cell. Biol. 14, 6683-6688
114. Gupta, S., Campbell, D., Derijard, B., and Davis, R. J. (1995) Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 267, 389-393
115. Coso, O. A., Chiarello, M., Kalinec, G., Kyriakis, J. M., Woodgett, J., and Gutkind, J. S. (1995) Transforming G protein-coupled receptors potently activate JNK (SAPK). Evidence for a divergence from the tyrosine kinase signaling pathway. J. Biol. Chem. 270, 5620-5624
116. Manser, E., Leung, T., Salihuddin, H., Zhao, Z., and Lira, L. (1994) A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature (London) 367, 40-46
117. Zachary, I., Sinnett-Smith, J., and Rozengurt, E. (1992) Bombesin, vasopressin and endothelin stimulation of tyrosine phosphorylation in Swiss 3T3 cells. J. Biol. Chem. 267, 19031-19034
118. FAK and p130 v-src substrate. Biochem. Biophys. Res. Commun. 188, 155-161
119. Roche, S., Koegel, M., and Courtneidge, S. A. (1994) The phosphatidylinositol 3-kinase alpha is required for DNA synthesis induced by some, but not all, growth factors. Proc. Natl. Acad. Sci. USA 91, 9185-9189
120. Weiss, R. H., and Maduri, M. (1993) The mitogenic effect of thrombin in vascular smooth muscle cells is largely due to basic fibroblast growth factor. J. Biol. Chem. 268, 5724-5727
121. Herbert, J.-M., Dupuy, E., Laplace, M.-C., Zini, J.-M., Bar Shavit, R., and Tobelem, G. (1994) Thrombin induces endothelial cell growth via both a proteolytic and a non-proteolytic pathway. Biochem. J. 303, 227-231
122. Hordijk, P. L., Verlaan, I., van Corven, E. J., and Moolenaar, W. H. (1994) Protein tyrosine phosphorylation induced by lysophosphatidic acid in rat-1 fibroblasts. J. Biol. Chem. 269, 645-651
123. 2+-induced regulation of ion channel and MAP kinase functions. Nature (London) 376, 737-745
124. Hansen, C. A., Schoering, A. G., Carey, D. J., and Robishaw, J.D. (1994) Localization of a heterotrimeric G protein γ subunit to focal adhesions and associated stress fibers. J. Cell Biol. 126, 811-819
125. Rozakis-Adcock, M., Fernley, R., Wade, J., Pawson, T., and Bowtell, D. (1993) The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1. Nature (London) 363, 83-85
126. Buday, L., and Downward, J. (1993) Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adaptor protein, and Sos nucleotide exchange factor. Cell 73, 611-620
127. Lowenstein, E. J., Daly, R. J., Batzer, A. G., Li, W., Margolis, B., Lammers, R., Ullrich, A., Skolnik, E. Y., Bar-Sagi, D., and Sehlessinger, J. (1992) The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 70, 431-442
128. Xu, N., McCormick, F., and Gutkind, J. S. (1994) The non-catalylic domain of ras-GAP inhibits transformation induced by G protein coupled receptors. Oncogene 9, 597-601
129. Mattingly, R. R., Sorisky, A., Brann, M. R., and Macara, I. G. (1995) Muscarinic receptors transform NIH 3T3 cells through a Ras-dependent signalling pathway inhibited by the Ras-GTPase-activating protein SH3 domain. Mol. Cell. Biol. 14, 7943-7952
130. Cantley, L. C., Auger, K. R., Carpenter, C., Duckworth, B., Graziani, A., Kapeller, R., and Solloff, S. (1991) Oncogenes and signal transduction. Cell 64, 281-302
131. Aaronson, S. A. (1991) Growth factors and cancel. Science 254, 1146-1153
132. Stephens, L., Smrcka, A., Cooke, F. T., Jackson, T. R., Sternweis, P. C., and Hawkins, P. T. (1994) A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated by G protein βγ subunits. Cell 77, 83-93
133. Stoyanov, B., Volinia, S., Hanck, T., Rubio, I., Loubtchenkov, M., Malek, D., Stoyanova, S., Vanhaesebroeck, B., Dhand, R., Nurnberg, B., Gierschik, P., Seedorf, K., Hsuan, J. J., Waterfield, M. D., and Wetzker, R. (1995) Cloning and characterization of a G-protein activated human phosphoinositide-3 kinase. Science 269, 690-693
134. Nakanishi, H., Brewer, K. A., and Exton, J. H. (1993) Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 268, 13-16
135. Berra, E., Diaz-Meco, M. T., Dominguez, I., Municio, M. M., Sanz, L., Lozano, J., Chapkin, R. S., and Moscat, J. (1993) Protein kinase C zeta isoform is critical for mitogenic signal transduction. Cell 74, 555-563
136. Gusovsky, F., Lueders, J. E., Kohn, E. C., and Felder, C. C. (1993) Muscarinic receptor-mediated tyrosine phosphorylation of phospholipase C-γ. J. Biol. Chem. 268, 7768-7772
137. Marrero, M. B., Paxton, W. G., Duff, J. L., Berk, B. C., and Bernstein, K. E. (1994) Angiotensin II stimulates tyrosine phosphorylation of phospholipase C-gamma 1 in vascular smooth muscle cells. J. Biol. Chem. 269, 10935-10939