Abstract
Heterotrimeric guanine nucleotide binding proteins, commonly known as G proteins form a super-family of signal transduction proteins. They are peripherally associated with the plasma membrane and provide signal coupling to seven transmembrane surface receptors. G proteins are composed of monomers of α, β, and γ subunits. The β- and γ-subunits are tightly associated. The receptors activated by the appropriate ‘signal’, interact catalytically with specific G-proteins to mediate guanine nucleotide exchange at the GDP/GTP binding site of the G-protein α-subunits, thus displacing the bound GDP for GTP. The GTP bound form of the g-protein α-subunit and in some cases the free βγ-subunits initiate cellular response by altering the activity of specific effector molecules. Recent studies have indicated that the asyncronous activation of these proteins can lead to the oncogenic transformation of different cell types. The mechanism by which G-proteins regulate the various cell functions appear to involve a complex net-working between different signaling pathways. This review summarizes the signaling mechanisms involved in the regulation of cell proliferation by these transforming G proteins.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Aktas H, Cai H, Cooper GM . 1997 Mol. Cell. Biol. 17: 3850–3857
Allen LF, Lefkowitz RJ, Caron MG, Cotecchia SG . 1991 Proc. Natl. Acad. Sci. USA 88: 4703–4707
Bourne HR . 1995 Nature 376: 727–729
Buhl AM, Johnson NL, Dhanasekaran N, Johnson GL . 1996 J. Biol. Chem. 270: 24631–24634
Burgering BM, Pronk GJ, van Weeren PC, Chardin P, Bos JL . 1993 EMBO J. 12: 4211–4220
Chan AN-L, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA . 1993 Mol. Cell Biol. 13: 762–768
Collins LR, Minden A, Karin M, Brown JH . 1996 J. Biol. Chem. 271: 17349–17353
Collins LR, Ricketts WA, Olefsky JM, Brown JH . 1997 Oncogene 15: 595–500
Conklin BR, Chabre O, Wong YH, Federman AD, Bourne HR . 1992 J. Biol. Chem. 267: 31–34
Cook SJ, McCormick F . 1993 Science 262: 1069–1072
Copeland NG, Zelenetz AD, Cooper GM . 1979 Cell 17: 993–1002
Dermott JM, Ramana Reddy MV, Djamila Onesime, Reddy EP, Dhanasekaran N . 1999 Oncogene 18: 7185–7189
Dermott JM, Dhanasekaran N . 2001 Meth. Enzymol in press
De Vivo M, Iyengar R . 1994 J. Biol. Chem. 269: 19671–19674
Dhanasekaran N, Dermott JM . 1996 Cell Signaling 8: 235–245
Dhanasekaran N, Heasley LE, Johnson GL . 1995 Endocrinol. Rev. 16: 259–270
Dhanasekaran N, Vara Prasad MVVS . 1998 Biol. Signals Recept. 7: 109–117
Dhanasekaran N, Vara Prasad MVVS, Wadsworth SJ, Dermott JM, van Rossum G . 1994 J. Biol. Chem. 269: 11802–11806
Dumont JE, Jauniaux JC, Roger PP . 1989 Trends Biochem. Sci. 14: 67–71
Fleming IN, Elliott CM, Collard JG, Exton JH . 1997 J. Biol. Chem. 272: 33105–33110
Fromm C, Coso OA, Montaner S, Xu N, Gutkind JS . 1997 Proc. Natl. Acad. Sci. USA 94: 10098–10103
Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS . 1999 J. Biol. Chem. 274: 5868–5879
Gohla A, Harhammer R, Schultz G . 1998 J. Biol. Chem. 273: 4653–4659
Gohla A, Offermanns S, Wilkie TM, Schultz G . 1999 J. Biol. Chem. 274: 17901–17907
Graves LM, Bornfeldt KE, Raines EW, Potts BC, Macdonald SG, Ross R, Krebs EG . 1993 Proc. Natl. Acad. Sci. USA 90: 10300–10304
Gupta SK, Gallego C, Johnson GL . 1992a Mol. Biol. Cell 3: 123–128
Gupta SK, Gallego C, Johnson GL, Heasley LE . 1992b J. Biol. Chem. 267: 7987–7990
Gupta SK, Gallego C, Lowndes JM, Pleiman CM, Sable C, Eisfelder BJ, Johnson GL . 1992c Mol. Cell Biol. 12: 190–197
Gutkind JS, Novotony EA, Brann MR, Robbins KC . 1991 Proc. Natl. Acad. Sci. USA 88: 4703–4707
Gutkind JS, Cosa OA, Xu N . 1998 G proteins, Receptors, and Diseases., AM Spiegal (ed.) Humana Press, NJ 101–117
Ham J, Ivan M, Wynford-Thomas D, Scanlon MF . 1997 Mol. Cell. Endocrinol. 127: 41–47
Hart JM, Jiang X, Kozasa T, Roscol W, Singer WD, Gilman AG, Sternweis PC, Bollag G . 1998 Science 280: 2112–2114
Hermouet S, Aznavoorian S, Spiegel AM . 1996 Cell. Signalling 8: 159–166
Hermouet S, de Mazancourt P, Spiegel AM . 1993 Cell. Signalling 5: 215–225
Heasley LE, Thaler S, Nicks M, Price B, Skorecki K, Nemenoff RA . 1997 J. Biol. Chem. 272: 14501–14504
Hill CS, Wynne J, Treisman R . 1995 Cell 81: 1159–1170
Hirai A, Nakamura S, Noguchi Y, Yasuda T, Kitagawa M, Tatsuno I, Oeda T, Tahara K, Terano T, Narumiya S, Kohn LD, Saito Y . 1997 J. Biol. Chem. 272: 13–16
Ho, Wong . 2001 Oncogene in press
Hooley R, Yu C-Y, Symons M, Barber DL . 1996 J. Biol. Chem. 271: 6152–6158
Jiang H, Wu D, Simon MI . 1993 FEBS Lett. 3: 319–322
Jiang Y, Ma W, Wan Y, Kozasa T, Haottori S, Huang XY . 1998 Nature 395: 808–813
Kalinec G, Nagaradi AJ, Hermouet S, Xu N, Gutkind JS . 1992 Mol. Cell. Biol. 12: 4687–4693
Kozasa T, Jiang X, Hart JM, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC . 1998 Science 280: 2109–2112
Kroll SD, Chen J, De Vivo M, Carty DJ, Baku A, Premont RT, Iyengar R . 1992 J. Biol. Chem. 267: 23183–23188
Kummer JL, Rao PK, Heidenreich KA . 1997 J. Biol. Chem. 272: 20490–20494
Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L . 1998 Nature 340: 692–696
Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J . 1995 Nature 376: 737–745
Lowndes JM, Gupta SK, Osawa S, Johnson GL . 1991 J. Biol. Chem. 266: 14193–14197
Lyons J, Landis CA, Hrash G, Vallar L, Grunewald K, Feichtinger H, Suk QY, Clark OH, Kawaski E, Bourne HR . 1990 Science 249: 655–659
Mao J, Yuan H, Xie W, Wu D . 1998a Proc. Natl. Acad. Sci. USA 95: 12973–12976
Mao J, Yan H, Xie W, Simon MI, Wu D . 1998b J. Biol. Chem. 273: 27118–27123
Mao J, Xie W, Yuan H, Simon MI, Mano H, Wu D . 1998c EMBO J. 17: 5638–5646
Marais R, Light Y, Mason C, Paterson H, Olson MF, Marshall CJ . 1998 Science 280: 109–112
Mischak H, Seitz T, Janosch P, Eulitz M, Steen H, Schellerer M, Philipp A, Kolch W . 1996 Mol. Cell. Biol. 16: 5409–5418
Mitsui H, Takuwa N, Kurokawa K, Exton JH, Takuwa Y . 1997 J. Biol. Chem. 272: 4904–4910
Moore KA, Sethi R, Doanes AM, Johnson TM, Pracyk JB, Kirby M, Irani K, Goldschmidt-Clermont PJ, Finkel T . 1997 Biochem. J. 326: 17–20
Muca C, Vallar L . 1994 Oncogene 9: 3647–3653
Nagao M, Kazino Y, Itah H . 1999 Oncogene 18: 4425–4434
Needham, LK, Rozengurt E . 1998 J. Biol. Chem. 273: 14626–14632
Olson MF, Ashworth A, Hall A . 1995 Science 269: 1270–1272
Pace AM, Wong YH, Bourne HR . 1991 Proc. Natl. Acad. Sci. USA 88: 7031–7035
Parks S, Wieschaus E . 1991 Cell 64: 447–458
Plonk SG, Park SK, Exton JH . 1998 J. Biol. Chem. 273: 4823–4826
Pouyssegur J, Seuwen K . 1992 Annu. Rev. Physiol. 54: 195–210
Ram P, Iyengar R . 2001 Oncogene in press
Reddy ST, Herschman HR . 1994 J. Biol. Chem. 269: 15473–15480
Ridley AJ, Hall A . 1992 Cell 70: 389–399
Schwindinger WF, Robishaw JD . 2001 Oncogene in press
Shi CS, Sinnarajah S, Cho H, Kozasa T, Kehrl JH . 2000 J. Biol. Chem. 275: 24470–24476
Sevetson BR, Kong X, Lawrence Jr JC . 1993 Proc. Natl. Acad. Sci. USA 90: 10305–10309
Slice LW, Walsh JH, Rozengurt E . 1999 J. Biol. Chem. 274: 27562–27566
Smith MR, Ryu SH, Suh PG, Rhee SG, Kung HFS . 1989 Proc. Natl. Acad. Sci. USA 86: 3659–3663
Strathman MP, Simon MI . 1991 Proc. Natl. Acad. Sci. USA 88: 5582–5586
Strathman M, Wilkie TM, Simon MI . 1989 Proc. Natl. Acad. Sci. USA 86: 7407–7409
Takai Y, Sasaki T, Tanaka K, Nakanishi H . 1995 Trends Biochem. Sci. 20: 227–231
Takuwa N, Takuwa Y . 1997 Mol. Cell. Biol. 17: 5348–5358
Tolkacheva T, Feuer B, Lorenzi MV, Saez R, Chan AML . 1997 Oncogene 15: 727–735
Tordjman K, Stern N, Ouaknine G, Yossiphov Y, Razon N, Nordenskjold M, Friedman E . 1993 J. Clin. Endocrinol. Meta. 77: 765–769
Vallar L . 1996 Cancer Sur. 27: 325–338
Vallar L, Spada A, Giannattasio G . 1987 Nature 330: 566–568
Van Biesen T, Luttrell LM, Hawse BE, Lefkowitz RJ . 1996 Endocrinol. Rev. 17: 698–714
Vara Prasad MVVS, Dermott JM, Heasley LE, Johnson GL, Dhanasekaran N . 1995 J. Biol. Chem. 270: 18655–18659
Vara Prasad MVVS, Shore SK, Dhanasekaran N . 1994 Oncogene 9: 2425–2429
Voyno-Yasenetskaya TA, Faur MP, Ahn NG, Bourne HR . 1996 J. Biol. Chem. 271: 21081–21087
Voyno-Yasenetskaya T, Pace AM, Bourne HR . 1994 Oncogene 9: 2559–2565
Wadsworth SJ, Gebauer G, van Rossum GDV, Dhanasekaran N . 1997 J. Biol. Chem. 272: 28829–28832
Winitz S, Russel M, Qian NX, Gardner A, Dwyer L, Johnson GL . 1993 J. Biol. Chem. 268: 19196–19199
Wong YH, Chan JSC, Yung LY, Bourne HR . 1995 Oncogene 10: 1927–1933
Wu J, Dent P, Jelinek T, Wolfman A, Weber MJ, Sturgill TW . 1993 Science 262: 1065–1069
Wu D, Lee CH, Rhee SG, Simon MI . 1992 J. Biol. Chem. 267: 1811–1817
Xu N, Bradley L, Ambudkar I, Gutkind JS . 1993 Proc. Natl. Acad. Sci. USA 90: 11354–11358
Xu N, Voyno-Yasenetskaya T, Gutkind JS . 1994 Biochem. Biophys. Res. Comm. 201: 603–609
Zachary I, Masters SB, Bourne HR . 1990 Biochem. Biophys. Res. Commun. 168: 1184–1193
Zeiger MA, Saji M, Caturegli P, Westra WH, Kohn LD, Levine MA . 1996 Endocrinology 137: 5392–5399
Zhang Y, Saez R, Leal MA, Chan AM . 1996 Oncogene 12: 2377–2383
Zou Y, Komuro I, Yamazaki T, Aikawa R, Kudoh S, Shiojima I, Hiroi Y, Mizuno T, Yazaki Y . 1996 J. Biol. Chem. 271: 33592–33597
Acknowledgements
The work was supported by the National Institutes of Health Grant GM49897 (N Dhanasekaran).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Radhika, V., Dhanasekaran, N. Transforming G proteins. Oncogene 20, 1607–1614 (2001). https://doi.org/10.1038/sj.onc.1204274
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204274
Keywords
This article is cited by
-
The involvement of the circFOXM1–miR–432–Gα12 axis in glioma cell proliferation and aggressiveness
Cell Death Discovery (2022)
-
The emerging roles of Gα12/13 proteins on the hallmarks of cancer in solid tumors
Oncogene (2022)
-
Mutations in G Protein Encoding Genes and Chromosomal Alterations in Primary Leptomeningeal Melanocytic Neoplasms
Pathology & Oncology Research (2015)
-
Mutations in G protein β subunits promote transformation and kinase inhibitor resistance
Nature Medicine (2015)
-
G protein-coupled receptors: novel targets for drug discovery in cancer
Nature Reviews Drug Discovery (2011)