Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Review Article

Rho GTPase-dependent transformation by G protein-coupled receptors

Oncogene volume 20, pages 1547–1555 (2001)Cite this article

Abstract

G protein coupled receptors (GPCRs) constitute the largest family of cell surface receptors, with more than 1000 members, and are responsible for converting a diverse array of extracellular stimuli into intracellular signaling events. Most members of the family have defined roles in intermediary metabolism and generally perform these functions in well-differentiated cells. However, there is an increasing awareness that some GPCRs can also regulate proliferative signaling pathways and that chronic stimulation or mutational activation of receptors can lead to oncogenic transformation. Activating mutations in GPCRs are associated with several types of human tumors and some receptors exhibit potent oncogenic activity due to agonist overexpression. Additionally, expression screening analyses for novel oncogenes identified GPCRs whose expression causes the oncogenic transformation of NIH3T3 mouse fibroblasts. These include Mas, G2A, and the PAR-1 thrombin receptor. In this review we summarize the signaling and transforming properties of these GPCR oncoproteins. What has emerged from these studies is the delineation of a GTPase cascade where transforming GPCRs cause aberrant growth regulation via activation of Rho family small GTPases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Allen LF, Lefkowitz RJ, Caron MG, Cotecchia S . 1991 Proc. Natl. Acad. Sci. USA. 88: 11354–11358

  • Aronheim A, Broder YC, Cohen A, Fritsch A, Belisle B, Abo A . 1998 Curr. Biol. 8: 1125–1128

  • Bishop AL, Hall A . 2000 Biochem. J. 348: 241–255

  • Bourne HR . 1997 Curr. Opin. Cell Biol. 9: 134–142

  • Brass LF, Ahuja M, Belmonte E, Pizarro S, Tarver A, Hoxie JA . 1998 The human platelet thrombin receptor. In Annals New York Academy of Sciences

  • Buhl AM, Johnson NL, Dhanasekaran N, Johnson GL . 1995 J. Biol. Chem. 270: 24631–24634

  • Cerione RA, Zheng Y . 1996 Curr. Opin. Cell Biol. 8: 216–222

  • Chan AML, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA . 1993 Mol. Cell. Biol. 13: 762–768

  • Chant J, Stowers L . 1995 Cell 81: 1–4

  • Chardin P . 1993 Structural conservation of ras-related proteins and its functional implications. In: GTPases in Biology I, Chapter 12. Dickey BF and Birnbaumer L. (eds) Springer-Verlag: Berlin Heidelberg

  • Clark EA, Golub TR, Lander ES, Hynes RO . 2000 Nature 406: 532–535

  • Coso OA, Chiariello M, Kalinec G, Kyriakis JM, Woodgett J, Gutkind JS . 1995b J. Biol. Chem. 270: 5620–5624

  • Coso OA, Chiariello M, Yu J-C, Teramoto H, Crespo P, Xu N, Miki T, Gutkind JS . 1995a Cell 81: 1137–1146

  • Coughlin SR . 1993 Thrombosis and Haemostasis 66: 184–187

  • Crespo P, Xu N, Simonds WF, Gutkind JS . 1994 Nature 379: 557–560

  • Cuttitta F, Carney DN, Mulshine J, Moody TW, Fedorko J, Fischler A, Minna JD . 1985 Nature 316: 823–826

  • del Peso L, Hernández-Alcoceba R, Embade N, Carnero A, Esteve P, Paje C, Lacal JC . 1998 Oncogene 15: 3047–3057

  • Dhanasekaran N, Tsim ST, Dermott JM, Onesime D . 1998 Oncogene 17: 1383–1394

  • Dohlman HG, Caron MG, Lefkowitz RJ . 1987 Biochemistry 26: 2657–2664

  • Ellis S, Mellor H . 2000 Curr. Biol. 10: 1387–1390

  • Even-Ram S, Uziely B, Cohen P, Grisaru-Granovsky S, Maoz M, Ginzburg Y, Reich R, Vlodavsky I, Bar-Shavit R . 1998 Nat. Med. 4: 909–914

  • Fukuhara S, Chikumi H, Gutkind JS . 2000 FEBS Lett 485: 183–188

  • Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS . 1999 J. Biol. Chem. 274: 5868–5879

  • Glaven JA, Whitehead IP, Nomanbhoy T, Kay R, Cerione RA . 1996 J. Biol. Chem. 271: 27374–27381

  • Gupta SK, Gallego C, Lowndes JM, Pleiman CM, Sable C, Eisfelder BJ, Johnson GL . 1992 Mol. Cell. Biol. 12: 190–197

  • Gutkind JS . 1998 J. Biol. Chem. 273: 1839–1842

  • Gutkind JS, Novotny EA, Brann MR, Robbins KC . 1991 Proc. Natl. Acad. Sci. USA 88: 4703–4707

  • Habets GGM, Scholtes EHM, Zuydgeest D, van der Kammen RA, Stam JC, Berns A, Collard JG . 1994 Cell 77: 537–549

  • Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G . 1998 Science 280: 2112–2114

  • Hart MJ, Sharma S, elMasry N, Qui R-G, McCabe P, Polakis P, Bollag G . 1996 J. Biol. Chem. 271: 25452–25458

  • Heasley LE, Storey B, Fanger GR, Butterfield L, Zamarripa J, Blumberg D, Maue RA . 1996 Mol. Cell. Biol. 16: 648–656

  • Henrikson KP, Salazar SL, Fenton JW, Pentecost BT . 1999 Br. J. Cancer 79: 401–406

  • Inglese J, Koch WJ, Touhara K, Lefkowitz RJ . 1995 Trends Biochem. Sci. 20: 151–161

  • Jiang H, Wu D, Simon MI . 1993 FEBS Lett. 330: 319–322

  • Julius D, Livelli TJ, Jessell TM, Axel R . 1989 Science 244: 1057–1062

  • Kabarowski J, Feramisco J, Le LQ, Gu J, Luoh S, Simon M, Witte ON . 2000 Proc. Natl. Acad. Sci. USA 97: 12109–12114

  • Keely PJ, Westwick JK, Whitehead IP, Der CJ, Parise LV . 1997 Nature 390: 632–636

  • Khosravi-Far R, Solski PA, Kinch MS, Burridge K, Der CJ . 1995 Mol. Cell. Biol. 15: 6443–6453

  • Koch WJ, Hawes BE, Allen LF, Lefkowitz RJ . 1994 Proc. Natl. Acad. Sci. USA 91: 12706–12710

  • Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS, Krahe R, Ruutu T, Knuutila S, Bloomfield CD, Caligiuri MA . 2000 Proc. Natl. Acad. Sci. USA 97: 2145–2150

  • Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC . 1998 Science 280: 2109–2111

  • Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L . 1989 Nature 340: 692–693

  • Lyons J, Landis CA, Harsh G, Vallar L, Grunewarld K, Feichtinger H, Duh Q-Y, Clark OH, Kawasaki E, Bourne HR, McCormick F . 1990 Science 249: 655–699

  • Mahmoud S, Staley J, Taylor J, Bogden A, Moreau JPI, Coy D, Avis I, Cuttitta F, Mulshine JL, Moody TW . 1991 Cancer Res. 51: 1798–1802

  • Mao J, Yuan H, Xie W, Wu D . 1998 Proc. Natl. Acad. Sci. USA 95: 12973–12976

  • Martin CB, Mahon GM, Klinger MB, Kay RJ, Symons M, Der CJ, Whitehead IP . 2001 Oncogene in press

  • Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG . 1995 Nature 375: 338–340

  • Monnot C, Weber V, Stinnakre J, Bihoreau C, Teutsch B, Corvol P, Clauser E . 1991 Mol. Endocrinol. 5: 1477–1487

  • Offermanns S, Heiler E, Spicher K, Schultz G . 1994 FEBS Lett. 349: 201–204

  • 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

  • Parma J, Duprey L, Van Sande J, Cochaux P, Gervy C, Mochel J, Dumont J, Vassart G . 1993 Nature 365: 649–651

  • Poyner DR, Hawkins PT, Benton HP, Hanley MR . 1990 Biochem. J. 271: 605–611

  • Prendergast GC, Khosravi-Far R, Solski PA, Kurzawa H, Lebowitz PF, Der CJ . 1995 Oncogene 10: 2289–2296

  • Qiu R-G, Abo A, McCormick F, Symons M . 1997 Mol. Cell. Biol. 17: 3449–3458

  • Qiu R-G, Chen J, Kirn D, McCormick F, Symons M . 1995a Nature 374: 457–459

  • Qiu R-G, Chen J, McCormick F, Symons M . 1995b Proc. Natl. Acad. Sci. USA 92: 11781–11785

  • Ridley AJ . 1996 Curr. Biol. 6: 1256–1264

  • Ridley AJ, Hall A . 1992 Cell 70: 389–399

  • Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A . 1992b Cell 70: 401–410

  • Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A . 1992a Cell 70: 401–410

  • Ross PC, Figler RA, Corjay MH, Barber CM, Adam N, Harcus DR, Lynch KR . 1990 Proc. Natl. Acad. Sci. USA 87: 3052–3056

  • Seasholtz TM, Majumdar M, Brown JH . 1999 Mol. Pharmacol. 55: 949–956

  • Seitz JF, Giovannini M, Gouvernet J, Gauthier M . 1991 J. Clin. Gastroenterol 13: 1541–1545

  • Shenker A, Lane L, Kosugi S, Merendino JJ, Minegiski T, Cutler GB . 1993 Nature 365: 652–654

  • Strader CD, Fong TM, Graziano MP, Tota MR . 1995 FASEB J 9: 745–754

  • Strader CD, Fong TM, Tota MR, Underwood D, Dixon RAF . 1994 Annu. Rev. Biochem. 63: 101–132

  • Symons M . 1995 Curr. Opin. Biotechnol. 6: 668–674

  • Symons M . 1996 Trends Biochem. Sci. 21: 178–181

  • Van Aelst L, D'Souza-Schorey C . 1997 Genes Dev. 11: 2295–2322

  • van Biesen T, Luttrell LM, Hawes BE, Lefkowitz RJ . 1996 Endocrine Rev. 17: 698–714

  • Van Obberghen-Schilling E, Pouysségur J . 1993 Thrombosis and Haemostasis 70: 163–167

  • Vara Prasad MVVS, Shore SK, Dhanasekaran N . 1994 Oncogene 9: 2425–2429

  • Vignal E, De Toledo M, Comunale F, Ladopoulou A, Gauthier-Rouviere C, Blangy A, Fort P . 2000 J. Biol. Chem. 275: 36457–36464

  • Voyno-Yasenetskaya TA, Pace AM, Bourne HR . 1994 Oncogene 9: 2559–2565

  • Weng Z, Fluckiger AC, Nisitani S, Wahl MI, Le LQ, Hunter CA, Fernal AA, Le Beau MM, Witte ON . 1998 Proc. Natl. Acad. Sci. USA 95: 12334–12339

  • Westwick JK, Lee RJ, Lambert QT, Symons M, Pestell RG, Der CJ, Whitehead IP . 1998 J. Biol. Chem. 273: 16739–16747

  • Whitehead IP, Campbell S, Rossman KL, Der CJ . 1997 Biochem. Biophys. Acta 1332: F1–F23

  • Whitehead IP, Khosravi-Far R, Kirk H, Trigo-Gonzalez G, Der CJ, Kay R . 1996 J. Biol. Chem. 271: 18643–18650

  • Whitehead IP, Kirk H, Kay R . 1995 Mol. Cell. Biol. 15: 704–710

  • Xu N, Bradley L, Ambdukar I, Gutkind JS . 1993 Proc. Natl. Acad. Sci. USA 90: 6741–6745

  • Xu Y, Fang X-J, Casey G, Mills GB . 1995 Biochem. J. 309: 933–940

  • Yamamoto M, Marui N, Sakai T, Morii N, Kozaki S, Ikai K, Imamura S, Narumiya S . 1993 Oncogene 8: 1449–1455

  • Young D, O'Neill K, Jessell T, Wigler M . 1988 Proc. Natl. Acad. Sci. USA 85: 5339–5342

  • Young D, Waitches G, Birchmeier C, Fasano O, Wigler M . 1986 Cell 45: 711–719

  • Zohn IE, Klinger M, Karp X, Kirk H, Symons M, Chrzanowska-Wodnicka M, Der CJ, Kay RJ . 2000 Oncogene 19: 3866–3877

  • Zohn IE, Symons M, Chrzanowska-Wodnicka M, Westwick JK, Der CJ . 1998b Mol. Cell Biol. 18: 1225–1235

  • Zohn IE, Yu H, Li X, Cox AD, Earp HS . 1995 Mol. Cell Biol. 15: 6160–6168

  • Zohn IE, Campbell SL, Khosravi-Far R, Rossman KL, Der CJ . 1998a Oncogene 17: 1415–1438

Download references

Acknowledgements

We thank Misha Rand for excellent assistance in preparation of the text, references and figures. Our studies were supported by Public Health Service grants CA42978, CA55008, CA63071 (CJ Der.) and CA77493 (IP Whitehead) from the National Cancer Institute.

Author information

Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, 07103-2714, New Jersey, NJ, USA

    Ian P Whitehead

  2. The Laboratory of Molecular Embryology, The Rockefeller University, 1230 York Avenue, Box 32, New York, 10021, NY, USA

    Irene E Zohn

  3. Department of Pharmacology, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, 27599-7295, NC, USA

    Channing J Der

Authors
  1. Ian P Whitehead
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irene E Zohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Channing J Der
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Whitehead, I., Zohn, I. & Der, C. Rho GTPase-dependent transformation by G protein-coupled receptors. Oncogene 20, 1547–1555 (2001). https://doi.org/10.1038/sj.onc.1204188

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204188

Keywords

This article is cited by

Search

Advanced search

Quick links