Abstract
Heterotrimeric G protein α,β, and γ subunits are subject to several kinds of co- and post-translational covalent modifications. Among those relevant to G protein-coupled receptor signaling in normal cell function are lipid modifications and phosphorylation. N-myristoylation is a co-translational modification occurring for members of the Gi family of Gα subunits, while palmitoylation is a post-translational modification that occurs for these and most other Gα subunits. One or both modifications are required for plasma membrane targeting and contribute to regulating strength of interaction with the Gβγ heterodimer, effectors, and regulators of G protein signaling (RGS proteins). Gα subunits, including those with transforming activity, are often inactive when unable to be modified with lipids. The reversible nature of palmitoylation is intriguing in this regard, as it lends itself to a regulation integrated with the activation state of the G protein. Several Gα subunits are substrates for phosphorylation by protein kinase C and at least one is a substrate for phosphorylation by the p21-activated protein kinase. Phosphorylation in both instances inhibits the interactions of these subunits with the Gβγ heterodimer and RGS proteins. Several Gα subunits are also substrates for tyrosine phosphorylation. A Gγ subunit is phosphorylated by protein kinase C, with the consequence that it interacts more tightly with a Gα subunit but less well with an effector.
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
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Anderson RGW . 1998 Ann. Rev. Biochem. 67: 199–225
Bañó MC, Jackson CS, Magee AI . 1998 Biochem. J. 330: 723–731
Berthiaume L, Resh MD . 1995 J. Biol. Chem. 270: 22399–22405
Bhamre S, Wang H-Y, Friedman E . 1998 J. Pharm. Exp. Ther. 286: 1482–1489
Bhatnagar RS, Gordon JI . 1997 Trends Cell Biol. 7: 14–20
Bhattacharyya R, Wedegaertner PB . 2000 J. Biol. Chem. 275: 14992–14999
Brown DA, London E . 1998 Ann. Rev. Cell Dev. Biol. 14: 111–136
Bushfield M, Murphy GJ, Lavan BE, Parker PJ, Hruby VJ, Milligan G, Houslay MD . 1990 Biochem. J. 268: 449–457
Cadwallader KA, Paterson H, MacDonald SG, Hancock JF . 1994 Mol. Cell. Biol. 14: 4722–4730
Carlson KE, Brass LF, Manning DR . 1989 J. Biol. Chem. 264: 13298–13305
Chang W-J, Ying Y, Rothberg KG, Hooper NM, Turner AJ, Gambliel HA, De Gunzburg J, Mumby SM, Gilman AG, Anderson RGW . 1994 J. Cell Biol. 126: 127–138
Chen CA, Manning DR . 2000 J. Biol. Chem. 275: 23516–23522
Daniel-Issakani S, Spiegel AM, Strulovici B . 1989 J. Biol. Chem. 264: 20240–20247
Das AK, Dasgupta B, Bhattacharyya R, Basu J . 1997 J. Biol. Chem. 272: 11021–11025
Degtyarev MY, Spiegel AM, Jones TLZ . 1993a Biochem. 32: 8057–8061
Degtyarev MY, Spiegel AM, Jones TLZ . 1993b J. Biol. Chem. 268: 23769–23772
Degtyarev MY, Spiegel AM, Jones TLZ . 1994 J. Biol. Chem. 269: 30898–30903
Duncan JA, Gilman AG . 1996 J. Biol. Chem. 271: 23594–23600
Duncan JA, Gilman AG . 1998 J. Biol. Chem. 273: 15830–15837
Dunphy JT, Greentree WK, Manahan CL, Linder ME . 1996 J. Biol. Chem. 271: 7154–7159
Dunphy JT, Linder ME . 1998 Biochim. Biophys. Acta 1436: 245–261
Evanko DS, Thiyagarajan MM, Wedegaertner PB . 2000 J. Biol. Chem. 275: 1327–1336
Fields TA, Casey PJ . 1995 J. Biol. Chem. 270: 23119–23125
Fishburn CS, Herzmark P, Morales J, Bourne HR . 1999 J. Biol. Chem. 274: 18793–18800
Fishburn CS, Pollitt SK, Bourne HR . 2000 Proc. Natl. Acad. Sci. USA 97: 1085–1090
Fu HW, Casey PJ . 1999 Rec. Prog. Hormone Res. 54: 315–342
Galbiati F, Guzzi F, Magee AI, Milligan G, Parenti M . 1994 Biochem. J. 303: 697–700
Galbiati F, Volonté D, Meani D, Milligan G, Lublin DM, Lisanti MP, Parenti M . 1999 J. Biol. Chem. 274: 5843–5850
Gallego C, Gupta SK, Winitz S, Eisfelder BJ, Johnson GL . 1992 Proc. Natl. Acad. Sci. USA 89: 9695–9699
Glick JL, Meigs TE, Miron A, Casey PJ . 1998 J. Biol. Chem. 273: 26008–26013
Gurdal H, Seacholtz TM, Wang H-Y, Brown RD, Johnson MD, Friedman E . 1997 Mol. Pharmacol. 52: 1064–1070
Hallak H, Brass LF, Manning DR . 1994a J. Biol. Chem. 269: 4571–4576
Hallak H, Muszbek L, Laposata M, Belmonte E, Brass LF, Manning DR . 1994b J. Biol. Chem. 269: 4713–4716
Hausdorff WP, Pitcher JA, Luttrell DK, Linder ME, Kurose H, Parsons SJ, Caron MG, Lefkowitz RJ . 1992 Proc. Natl. Acad. Sci. USA 89: 5720–5724
Hepler JR, Biddlecome GH, Kleuss C, Camp LA, Hofmann SL, Ross EM, Gilman AG . 1996 J. Biol. Chem. 271: 496–504
Hohenegger M, Mitterauer T, Voss T, Nanoff C, Freissmuth M . 1996 Mol. Pharmacol. 49: 73–80
Huang C, Duncan JA, Gilman AG, Mumby SM . 1999 Proc. Natl. Acad. Sci. USA 96: 412–417
Huang C, Hepler JR, Chen LT, Gilman AG, Anderson RGW, Mumby SM . 1997 Mol. Biol. Cell 8: 2365–2378
Iiri T, Backlund PS, Jones TLZ, Wedegaertner PB, Bourne HR . 1996 Proc. Natl. Acad. Sci. USA 93: 14592–14597
Johnson DR, Bhatnagar RS, Knnoll LJ, Gordon JI . 1994 Annu. Rev. Biochem. 63: 869–914
Jones TLZ, Gutkind JS . 1998 Biochem. 37: 3196–3202
Jones TLZ, Simonds WF, Merendino JJ, Brann MR, Spiegel AM . 1990 Proc. Natl. Acad. Sci. USA 87: 568–572
Katada T, Gilman AG, Watanabe Y, Bauer S, Jakobs KH . 1985 Eur. J. Biochem. 151: 431–437
Kleuss C, Gilman AG . 1997 Proc. Natl. Acad. Sci. USA 94: 6116–6120
Klinker JF, Seifert R . 1999 Eur. J. Biochem. 261: 72–80
Kozasa T, Gilman AG . 1996 J. Biol. Chem. 271: 12562–12567
Krupinski J, Rajaram R, Lakonishok M, Benovic JL, Cerione RA . 1988 J. Biol. Chem. 263: 12333–12341
Linder ME, Pang I-H, Duronio RJ, Gordon JI, Sternweis PC, Gilman AG . 1991 J. Biol. Chem. 266: 4654–4659
Lisanti MP, Scherer PE, Vidugiriene J, Tang Z, Hermanowski-Vosatka A, Tu Y-H, Cook RF, Sargiacomo M . 1994 J. Cell Biol. 126: 111–126
Liu WW, Mattingly RR, Garrison JC . 1996 Proc. Natl. Acad. Sci. USA 93: 8258–8263
Loisel TP, Ansanay H, Adam L, Marullo S, Seifer R, Lagace M, Bouvier M . 1999 J. Biol. Chem. 274: 31014–31019
Lounsbury KM, Casey PJ, Brass LF, Manning DR . 1991 J. Biol. Chem. 266: 22051–22056
Lounsbury KM, Schlegel B, Poncz M, Brass LF, Manning DR . 1993 J. Biol. Chem. 268: 3494–3498
Milligan G, Parenti M, Magee AI . 1995 Trends Biochem. Sci. 20: 181–186
Moffett S, Brown DA, Linder ME . 2000 J. Biol. Chem. 275: 2191–2198
Morales J, Fishburn CS, Wilson PT, Bourne HR . 1998 Mol. Biol. Cell 9: 1–14
Morishita R, Nakayama H, Isobe T, Matsuda T, Hashimoto Y, Okano T, Fukada Y, Mizuno K, Ohno S, Kozawa O, Kata K, Asano T . 1995 J. Biol. Chem. 270: 29469–29475
Moyers JS, Linder ME, Shannon JD, Parsons SJ . 1995 Biochem. J. 305: 411–417
Mumby SM . 1997 Curr. Opin. Cell Biol. 9: 148–154
Mumby SM, Heukeroth RO, Gordon JI, Gilman AG . 1990 Proc. Natl. Acad. Sci. USA 87: 728–732
Mumby SM, Kleuss C, Gilman AG . 1994 Proc. Natl. Acad. Sci. USA 91: 2800–2804
Neubert TA, Johnson RS, Hurley JB, Walsh KA . 1992 J. Biol. Chem. 267: 18274–18277
O'Brien PJ, St. Jules RS, Reddy TS, Bazan NG, Zatz M . 1987 J. Biol. Chem. 262: 5210–5215
Offermanns S, Hu Y-H, Simon MI . 1996 J. Biol. Chem. 271: 26044–26048
Peitzsch RM, McLaughlin S . 1993 Biochem. 32: 10436–10443
Resh MD . 1996 Cell Signaling 8: 403–412
Ross EM . 1995 Curr. Biol. 5: 107–109
Schnitzer JE, Liu J, Oh P . 1995 J. Biol. Chem. 270: 14399–14404
Schroeder H, Leventis R, Shahinian S, Walton PA, Silvius JR . 1996 J. Cell Biol. 134: 647–660
Shahinian S, Silvius JR . 1995 Biochem. 34: 3813–3822
Smart EJ, Graf GA, McNiven MA, Sessa WC, Engelman JA, Scherer PE, Okamoto T, Lisanti MP . 1999 Mol. Cell. Biol. 19: 7289–7304
Smart EJ, Ying Y-S, Mineo C, Anderson RGW . 1995 Proc. Natl. Acad. Sci. USA 92: 10104–10108
Song KS, Sargiacomo M, Galbiati F, Parenti M, Lisanti MP . 1997 Cell. Mol. Biol. 43: 292–303
Stanislaus D, Janovick JA, Brothers S, Conn PM . 1997 Mol. Endocrinol. 11: 738–746
Stanislaus D, Ponder S, Ji TH, Conn PM . 1998 Biol. Repro. 59: 579–586
Strassheim D, Malbon CC . 1994 J. Biol. Chem. 269: 14307–14313
Taussig R, Iñiguez-Lluhi JA, Gilman AG . 1993 Science 261: 218–221
Tu Y, Wang J, Ross EM . 1997 Science 278: 1132–1135
Ueda H, Yamauchi J, Itoh H, Morishita R, Kaziro Y, Kato K, Asano T . 1999 J. Biol. Chem. 274: 12124–12128
Umemori H, Inoue T, Kume S, Sekiyama N, Nagao M, Itoh H, Nakanishi S, Mikoshiba K, Yamamoto T . 1997 Science 276: 1878–1881
Wang J, Ducret A, Tu Y, Kozasa T, Aebersold R, Ross EM . 1998 J. Biol. Chem. 273: 26014–26025
Wang J, Frost JA, Cobb MH, Ross RM . 1999a J. Biol. Chem. 274: 31641–31647
Wang Y, Windh RT, Chen CA, Manning DR . 1999b J. Biol. Chem. 274: 37435–37442
Wedegaertner PB . 1998 Biol. Signals Receptors 7: 125–135
Wedegaertner PB, Bourne HR . 1994 Cell 77: 1063–1070
Wedegaertner PB, Bourne HR, von Zastrow M . 1996 Mol. Biol. Cell 7: 1225–1233
Wedegaertner PB, Chu DH, Wilson PT, Levis MJ, Bourne HR . 1993 J. Biol. Chem. 268: 25001–25008
Wedegaertner PB, Wilson PT, Bourne HR . 1995 J. Biol. Chem. 270: 503–506
Wieland T, Nürnberg B, Ulibarri I, Kaldenberg-Stasch S, Schultz G, Jakobs KH . 1993 J. Biol. Chem. 268: 18111–18118
Wieland T, Ronzani M, Jakobs KH . 1992 J. Biol. Chem. 267: 20791–20797
Wieland T, Ulibarri I, Gierschik P, Jakobs KH . 1991 Eur. J. Biochem. 196: 707–716
Wise A, Parenti M, Milligan G . 1997 FEBS Lett. 407: 257–260
Yasuda H, Lindorfer MA, Myung C-S, Garrison JC . 1998 J. Biol. Chem. 273: 21958–21965
Zick Y, Sagi-Eisenberg R, Pines M, Gierschik P, Spiegel AM . 1986 Proc. Natl. Acad. Sci. USA 83: 9294–9297
Acknowledgements
The authors wish to acknowledge the support of NIH grant GM51196.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chen, C., Manning, D. Regulation of G proteins by covalent modification. Oncogene 20, 1643–1652 (2001). https://doi.org/10.1038/sj.onc.1204185
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204185
Keywords
This article is cited by
-
Local and substrate-specific S-palmitoylation determines subcellular localization of Gαo
Nature Communications (2022)
-
Protein N-myristoylation: functions and mechanisms in control of innate immunity
Cellular & Molecular Immunology (2021)
-
The Gαi protein subclass selectivity to the dopamine D2 receptor is also decided by their location at the cell membrane
Cell Communication and Signaling (2020)
-
Protein expression of prenyltransferase subunits in postmortem schizophrenia dorsolateral prefrontal cortex
Translational Psychiatry (2020)
-
Negative feedback-loop mechanisms regulating HOG- and pheromone-MAPK signaling in yeast
Current Genetics (2020)