|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 39, 30211-30219, September 29, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Physiology and Medicine, Medical College of
Virginia, Virginia Commonwealth University,
Richmond, Virginia 23298-0711
We examined the notion that sequestration of G
protein subunits by binding to caveolin impedes G protein reassociation
and leads to transient, G protein-specific desensitization of response in dispersed smooth muscle cells. Cholecystokinin octapeptide (CCK-8) and substance P (SP) were used to activate
Gq/11, cyclopentyl adenosine (CPA) was used to
activate Gi3, and acetylcholine (ACh) was used to activate
both Gq/11 and Gi3 via m3 and m2 receptors, respectively. CCK-8 and SP increased only G
Heterologous Desensitization Mediated by G Protein-specific
Binding to Caveolin*
and
q/11, and CPA
increased only Gi3 in caveolin immunoprecipitates;
caveolin and other G proteins were not increased. ACh increased both
Gq/11 and Gi3 in a time- and
concentration-dependent fashion: only Gq/11
was increased in the presence of an m2 antagonist, and only
Gi3 was increased in the presence of an m3 antagonist.
To determine whether transient G protein binding to caveolin affected
subsequent responses mediated by the same G protein, PLC-
activity
was measured in cells stimulated sequentially with two different
agonists that activate either the same or a different G protein. After
treatment of the cells with ACh and an m2 antagonist, the phospholipase C- (PLC-) response to CCK-8 and SP, but not CPA, was decreased; conversely, after treatment of the cells with ACh and an m3 antagonist, the PLC- response to CPA, but not CCK-8 or SP, was decreased. Similarly, after treatment with CCK-8 or SP, the PLC- response mediated by Gq/11 only was decreased, whereas after
treatment with CPA, the PLC- response mediated by Gi3
only was decreased. A caveolin-binding Gq/11 fragment
blocked the binding of activated Gq/11 but not
Gi3 to caveolin-3 and prevented desensitization of the
PLC- response mediated only by other Gq/11-coupled
receptors. A caveolin-binding Gi3 fragment had the
reverse effect. Thus, transient binding of receptor-activated G protein
subunits to caveolin impedes reassociation of the heterotrimeric
species and leads to desensitization of response mediated by other
receptors coupled to the same G protein.
*
This work was supported by Grant DK15564 from the NIDDK,
National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: P.O. Box 980711, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0711. Tel.: 804-828-8504; Fax:
804-828-2500; skarnam@hsc.vcu.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. S. Murthy, S. Mahavadi, J. Huang, H. Zhou, and W. Sriwai Phosphorylation of GRK2 by PKA augments GRK2-mediated phosphorylation, internalization, and desensitization of VPAC2 receptors in smooth muscle Am J Physiol Cell Physiol, February 1, 2008; 294(2): C477 - C487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gosens, G. L. Stelmack, G. Dueck, M. M. Mutawe, M. Hinton, K. D. McNeill, A. Paulson, S. Dakshinamurti, W. T. Gerthoffer, J. A. Thliveris, et al. Caveolae facilitate muscarinic receptor-mediated intracellular Ca2+ mobilization and contraction in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1406 - L1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Xiao, F. Schmitz, V. E. Pricolo, P. Biancani, and J. Behar Role of caveolae in the pathogenesis of cholesterol-induced gallbladder muscle hypomotility Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1641 - G1649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gosens, G. Dueck, W. T. Gerthoffer, H. Unruh, J. Zaagsma, H. Meurs, and A. J. Halayko p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1163 - L1172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huang, H. Zhou, S. Mahavadi, W. Sriwai, and K. S. Murthy Inhibition of G{alpha}q-dependent PLC-beta1 activity by PKG and PKA is mediated by phosphorylation of RGS4 and GRK2 Am J Physiol Cell Physiol, January 1, 2007; 292(1): C200 - C208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shakirova, J. Bonnevier, S. Albinsson, M. Adner, B. Rippe, J. Broman, A. Arner, and K. Sward Increased Rho activation and PKC-mediated smooth muscle contractility in the absence of caveolin-1. Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1326 - C1335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Fischmeister, L. R.V. Castro, A. Abi-Gerges, F. Rochais, J. Jurevicius, J. Leroy, and G. Vandecasteele Compartmentation of Cyclic Nucleotide Signaling in the Heart: The Role of Cyclic Nucleotide Phosphodiesterases Circ. Res., October 13, 2006; 99(8): 816 - 828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Remillard and J. X.-J. Yuan Transient Receptor Potential Channels and Caveolin-1: Good Friends in Tight Spaces Mol. Pharmacol., October 1, 2006; 70(4): 1151 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Xu, S.-I. Yoon, P. Huang, Y. Wang, C. Chen, P. L.-G. Chong, and L.-Y. Liu-Chen Localization of the {kappa} Opioid Receptor in Lipid Rafts J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1295 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Rudajev, J. Novotny, L. Hejnova, G. Milligan, and P. Svoboda Dominant Portion of Thyrotropin-Releasing Hormone Receptor Is Excluded from Lipid Domains. Detergent-Resistant and Detergent-Sensitive Pools of TRH Receptor and Gq{alpha}/G11{alpha} Protein J. Biochem., August 1, 2005; 138(2): 111 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Dabisch, D. B. Miller, S. A. Reutter, R. J. Mioduszewski, and S. A. Thomson Miotic Tolerance to Sarin Vapor Exposure: Role of the Sympathetic and Parasympathetic Nervous Systems Toxicol. Sci., June 1, 2005; 85(2): 1041 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Gratton, P. Bernatchez, and W. C. Sessa Caveolae and Caveolins in the Cardiovascular System Circ. Res., June 11, 2004; 94(11): 1408 - 1417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Minshall, W. C. Sessa, R. V. Stan, R. G. W. Anderson, and A. B. Malik Caveolin regulation of endothelial function Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1179 - L1183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Kifor, I. Kifor, F. D. Moore Jr., R. R. Butters Jr., and E. M. Brown m-Calpain Colocalizes with the Calcium-sensing Receptor (CaR) in Caveolae in Parathyroid Cells and Participates in Degradation of the CaR J. Biol. Chem., August 15, 2003; 278(33): 31167 - 31176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. GRATZINGER, S. CANOSA, B. ENGELHARDT, and J. A. MADRI Platelet endothelial cell adhesion molecule-1 modulates endothelial cell motility through the small G-protein Rho FASEB J, August 1, 2003; 17(11): 1458 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Manganello, J.-S. Huang, T. Kozasa, T. A. Voyno-Yasenetskaya, and G. C. Le Breton Protein Kinase A-mediated Phosphorylation of the Galpha 13 Switch I Region Alters the Galpha beta gamma 13-G Protein-coupled Receptor Complex and Inhibits Rho Activation J. Biol. Chem., January 3, 2003; 278(1): 124 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sabourin, L. Bastien, D. R. Bachvarov, and F. Marceau Agonist-Induced Translocation of the Kinin B1 Receptor to Caveolae-Related Rafts Mol. Pharmacol., March 1, 2002; 61(3): 546 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Razani and M. P. Lisanti Two distinct caveolin-1 domains mediate the functional interaction of caveolin-1 with protein kinase A Am J Physiol Cell Physiol, October 1, 2001; 281(4): C1241 - C1250. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |