![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 9, Issue 1, 1-14, January 1998
z Requires
Two Signals
Departments of Cellular and Molecular Pharmacology and Medicine and
the Cardiovascular Research Institute, University of California, San
Francisco, California 94143
Three covalent attachments anchor heterotrimeric G proteins to
cellular membranes: the 
subunits are myristoylated and/or palmitoylated, whereas the 
chain is prenylated. Despite the essential role of these modifications in membrane attachment, it is not
clear how they cooperate to specify G protein localization at the
plasma membrane, where the G protein relays signals from cell surface
receptors to intracellular effector molecules. To explore this
question, we studied the effects of mutations that prevent
myristoylation and/or palmitoylation of an epitope-labeled subunit,
z. Wild-type z (z-WT)
localizes specifically at the plasma membrane. A mutant that
incorporates only myristate is mistargeted to intracellular membranes,
in addition to the plasma membrane, but transduces hormonal signals as
well as does z-WT. Removal of the myristoylation site
produced a mutant z that is located in the cytosol, is
not efficiently palmitoylated, and does not relay the hormonal signal.
Coexpression of 
with this myristoylation defective mutant
transfers it to the plasma membrane, promotes its palmitoylation, and
enables it to transmit hormonal signals. Pulse-chase experiments show
that the palmitate attached to this myristoylation-defective mutant
turns over much more rapidly than does palmitate on
z-WT, and that the rate of turnover is further
accelerated by receptor activation. In contrast, receptor activation
does not increase the slow rate of palmitate turnover on
z-WT. Together these results suggest that myristate and
promote stable association with membranes not only by providing hydrophobicity, but also by stabilizing attachment of palmitate. Moreover, palmitoylation confers on z specific
localization at the plasma membrane.
This article has been cited by other articles:
|
|
 |
|
  J. M. Draper, Z. Xia, and C. D. Smith Cellular palmitoylation and trafficking of lipidated peptides J. Lipid Res., August 1, 2007; 48(8): 1873 - 1884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Resh Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules Sci. Signal., October 31, 2006; 2006(359): re14 - re14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Harashima and J. Heitman G{alpha} Subunit Gpa2 Recruits Kelch Repeat Subunits That Inhibit Receptor-G Protein Coupling during cAMP-induced Dimorphic Transitions in Saccharomyces cerevisiae Mol. Biol. Cell, October 1, 2005; 16(10): 4557 - 4571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Hoffman Except in Every Detail: Comparing and Contrasting G-Protein Signaling in Saccharomyces cerevisiae and Schizosaccharomyces pombe Eukaryot. Cell, March 1, 2005; 4(3): 495 - 503. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dutt, A. B. Jaffe, K. D. Merdek, A. Hall, and D. Toksoz G{alpha}z Inhibits Serum Response Factor-Dependent Transcription by Inhibiting Rho Signaling Mol. Pharmacol., December 1, 2004; 66(6): 1508 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, T. S. Gray, D. N. D'Souza, G. A. Carrasco, K. J. Damjanoska, B. Dudas, F. Garcia, G. M. Zainelli, N. R. Sullivan Hanley, G. Battaglia, et al. Desensitization of 5-HT1A Receptors by 5-HT2A Receptors in Neuroendocrine Neurons in Vivo J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 59 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Takida and P. B. Wedegaertner Heterotrimer Formation, Together with Isoprenylation, Is Required for Plasma Membrane Targeting of Gbeta gamma J. Biol. Chem., May 2, 2003; 278(19): 17284 - 17290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Z. Scheifele, J. D. Rhoads, and L. J. Parent Specificity of Plasma Membrane Targeting by the Rous Sarcoma Virus Gag Protein J. Virol., January 1, 2003; 77(1): 470 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Meng and P. J. Casey Activation of Gz Attenuates Rap1-mediated Differentiation of PC12 Cells J. Biol. Chem., November 1, 2002; 277(45): 43417 - 43424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Michaelson, I. Ahearn, M. Bergo, S. Young, and M. Philips Membrane Trafficking of Heterotrimeric G Proteins via the Endoplasmic Reticulum and Golgi Mol. Biol. Cell, September 1, 2002; 13(9): 3294 - 3302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, D. D'Souza, D. K. Raap, F. Garcia, G. Battaglia, N. A. Muma, and L. D. Van de Kar Characterization of the Functional Heterologous Desensitization of Hypothalamic 5-HT1A Receptors after 5-HT2A Receptor Activation J. Neurosci., October 15, 2001; 21(20): 7919 - 7927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rondard, T. Iiri, S. Srinivasan, E. Meng, T. Fujita, and H. R. Bourne Mutant G protein alpha subunit activated by Gbeta gamma : A model for receptor activation? PNAS, May 3, 2001; (2001) 101136198. [Abstract] [Full Text]
|
|
|
|
|
|
P. H. Tso and Y. H. Wong Gz Can Mediate the Acute Actions of {micro}- and kappa -Opioids but Is Not Involved in Opioid-Induced Adenylyl Cyclase Supersensitization J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 168 - 176. [Abstract] [Full Text]
|
|
|
|
|
|
P. W. Denny, S. Gokool, D. G. Russell, M. C. Field, and D. F. Smith Acylation-dependent Protein Export in Leishmania J. Biol. Chem., April 6, 2000; 275(15): 11017 - 11025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Manahan, M. Patnana, K. J. Blumer, and M. E. Linder Dual Lipid Modification Motifs in Galpha and Ggamma Subunits Are Required for Full Activity of the Pheromone Response Pathway in Saccharomyces cerevisiae Mol. Biol. Cell, March 1, 2000; 11(3): 957 - 968. [Abstract] [Full Text]
|
|
|
|
|
|
C. S. Fishburn, S. K. Pollitt, and H. R. Bourne Localization of a peripheral membrane protein: Gbeta gamma targets Galpha Z PNAS, February 1, 2000; 97(3): 1085 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Moffett, D. A. Brown, and M. E. Linder Lipid-dependent Targeting of G Proteins into Rafts J. Biol. Chem., January 21, 2000; 275(3): 2191 - 2198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Evanko, M. M. Thiyagarajan, and P. B. Wedegaertner Interaction with Gbeta gamma Is Required for Membrane Targeting and Palmitoylation of Galpha s and Galpha q J. Biol. Chem., January 14, 2000; 275(2): 1327 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, R. T. Windh, C. A. Chen, and D. R. Manning N-Myristoylation and beta gamma Play Roles beyond Anchorage in the Palmitoylation of the G Protein alpha o Subunit J. Biol. Chem., December 24, 1999; 274(52): 37435 - 37442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. McCabe and L. G. Berthiaume Functional Roles for Fatty Acylated Amino-terminal Domains in Subcellular Localization Mol. Biol. Cell, November 1, 1999; 10(11): 3771 - 3786. [Abstract] [Full Text]
|
|
|
|
|
|
T. P. Loisel, H. Ansanay, L. Adam, S. Marullo, R. Seifert, M. Lagace, and M. Bouvier Activation of the beta 2-Adrenergic Receptor-Galpha s Complex Leads to Rapid Depalmitoylation and Inhibition of Repalmitoylation of Both the Receptor and Galpha s J. Biol. Chem., October 22, 1999; 274(43): 31014 - 31019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gonzalo, W. K. Greentree, and M. E. Linder SNAP-25 Is Targeted to the Plasma Membrane through a Novel Membrane-binding Domain J. Biol. Chem., July 23, 1999; 274(30): 21313 - 21318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Fishburn, P. Herzmark, J. Morales, and H. R. Bourne Gbeta gamma and Palmitate Target Newly Synthesized Galpha z to the Plasma Membrane J. Biol. Chem., June 25, 1999; 274(26): 18793 - 18800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Druey, O. Ugur, J. M. Caron, C.-K. Chen, P. S. Backlund, and T. L. Z. Jones Amino-terminal Cysteine Residues of RGS16 Are Required for Palmitoylation and Modulation of Gi- and Gq-mediated Signaling J. Biol. Chem., June 25, 1999; 274(26): 18836 - 18842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Galbiati, D. Volonte, D. Meani, G. Milligan, D. M. Lublin, M. P. Lisanti, and M. Parenti The Dually Acylated NH2-terminal Domain of Gi1alpha Is Sufficient to Target a Green Fluorescent Protein Reporter to Caveolin-enriched Plasma Membrane Domains. PALMITOYLATION OF CAVEOLIN-1 IS REQUIRED FOR THE RECOGNITION OF DUALLY ACYLATED G-PROTEIN alpha SUBUNITS IN VIVO J. Biol. Chem., February 26, 1999; 274(9): 5843 - 5850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Huang, J. A. Duncan, A. G. Gilman, and S. M. Mumby Persistent membrane association of activated and depalmitoylated G protein alpha subunits PNAS, January 19, 1999; 96(2): 412 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bhattacharyya and P. B. Wedegaertner Galpha 13 Requires Palmitoylation for Plasma Membrane Localization, Rho-dependent Signaling, and Promotion of p115-RhoGEF Membrane Binding J. Biol. Chem., May 12, 2000; 275(20): 14992 - 14999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Chen and D. R. Manning Regulation of Galpha i Palmitoylation by Activation of the 5-Hydroxytryptamine-1A Receptor J. Biol. Chem., July 28, 2000; 275(31): 23516 - 23522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rondard, T. Iiri, S. Srinivasan, E. Meng, T. Fujita, and H. R. Bourne Mutant G protein alpha subunit activated by Gbeta gamma : A model for receptor activation? PNAS, May 22, 2001; 98(11): 6150 - 6155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. X. Lu and E. M. Hrabak An Arabidopsis Calcium-Dependent Protein Kinase Is Associated with the Endoplasmic Reticulum Plant Physiology, March 1, 2002; 128(3): 1008 - 1021. [Abstract] [Full Text] [PDF]
|
|
