HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 34, 30236-30241, August 26, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/34/30236    most recent M500722200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Natochin, M. Articles by Braun, J. E. A. Search for Related Content PubMed PubMed Citation Articles by Natochin, M. Articles by Braun, J. E. A. Social Bookmarking                      What's this?

Characterization of the G_s Regulator Cysteine String Protein^*

Michael Natochin, Tessa N. Campbell, Brandy Barren, Linda C. Miller, Shahid Hameed, Nikolai O. Artemyev, and Janice E. A. Braun, Recipient of a CIHR New Investigator award and an Alberta Heritage Foundation for Medical Research scholar¶

From the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada and Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52254

Cysteine string protein (CSP) is an abundant regulated secretory vesicle protein that is composed of a string of cysteine residues, a linker domain, and an N-terminal J domain characteristic of the DnaJ/Hsp40 co-chaperone family. We have shown previously that CSP associates with heterotrimeric GTP-binding proteins (G proteins) and promotes G protein inhibition of N-type Ca²⁺ channels. To elucidate the mechanisms by which CSP modulates G protein signaling, we examined the effects of CSP_1–198 (full-length), CSP_1–112, and CSP_1–82 on the kinetics of guanine nucleotide exchange and GTP hydrolysis. In this report, we demonstrate that CSP selectively interacts with G_s and increases steady-state GTP hydrolysis. CSP_1–198 modulation of G_s was dependent on Hsc70 (70-kDa heat shock cognate protein) and SGT (small glutamine-rich tetratricopeptide repeat domain protein), whereas modulation by CSP_1–112 was Hsc70-SGT-independent. CSP_1–112 preferentially associated with the inactive GDP-bound conformation of G_s. Consistent with the stimulation of GTP hydrolysis, CSP_1–112 increased guanine nucleotide exchange of G_s. The interaction of native G_s and CSP was confirmed by coimmunoprecipitation and showed that G_s associates with CSP. Furthermore, transient expression of CSP in HEK cells increased cellular cAMP levels in the presence of the ₂ adrenergic agonist isoproterenol. Together, these results demonstrate that CSP modulates G protein function by preferentially targeting the inactive GDP-bound form of G_s and promoting GDP/GTP exchange. Our results show that the guanine nucleotide exchange activity of full-length CSP is, in turn, regulated by Hsc70-SGT.

Received for publication, January 20, 2005 , and in revised form, June 21, 2005.

^* This work was supported in part by operating grants from the Canadian Institutes of Health Research (CIHR) (to J. E. A. B.) and by National Institutes of Health Grant RO1 EY-12682 (to N. O. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This 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: Hotchkiss Brain Inst., University of Calgary, 3330 Hospital Dr. N.W., Calgary, Alberta T2N 4N1, Canada.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Weng, M. D. Baumler, D. D. H. Thomas, M. A. Falkowski, L. A. Swayne, J. E. A. Braun, and G. E. Groblewski Functional role of J domain of cysteine string protein in Ca2+-dependent secretion from acinar cells Am J Physiol Gastrointest Liver Physiol, May 1, 2009; 296(5): G1030 - G1039. [Abstract] [Full Text] [PDF]

				M. Garcia-Marcos, P. Ghosh, and M. G. Farquhar GIV is a nonreceptor GEF for G{alpha}i with a unique motif that regulates Akt signaling PNAS, March 3, 2009; 106(9): 3178 - 3183. [Abstract] [Full Text] [PDF]

				B. Z. Schmidt, R. J. Watts, M. Aridor, and R. A. Frizzell Cysteine String Protein Promotes Proteasomal Degradation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Increasing Its Interaction with the C Terminus of Hsp70-interacting Protein and Promoting CFTR Ubiquitylation J. Biol. Chem., February 13, 2009; 284(7): 4168 - 4178. [Abstract] [Full Text] [PDF]

				E. Meimaridou, S. B Gooljar, and J P. Chapple From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery J. Mol. Endocrinol., January 1, 2009; 42(1): 1 - 9. [Abstract] [Full Text] [PDF]

				A. Plagge, G. Kelsey, and E. L Germain-Lee Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse J. Endocrinol., February 1, 2008; 196(2): 193 - 214. [Abstract] [Full Text] [PDF]

				G. Buchanan, C. Ricciardelli, J. M. Harris, J. Prescott, Z. C.-L. Yu, L. Jia, L. M. Butler, V. R. Marshall, H. I. Scher, W. L. Gerald, et al. Control of Androgen Receptor Signaling in Prostate Cancer by the Cochaperone Small Glutamine Rich Tetratricopeptide Repeat Containing Protein {alpha} Cancer Res., October 15, 2007; 67(20): 10087 - 10096. [Abstract] [Full Text] [PDF]

				D. J. Dupre, M. Robitaille, M. Richer, N. Ethier, A. M. Mamarbachi, and T. E. Hebert Dopamine Receptor-interacting Protein 78 Acts as a Molecular Chaperone for G{gamma} Subunits before Assembly with Gbeta J. Biol. Chem., May 4, 2007; 282(18): 13703 - 13715. [Abstract] [Full Text] [PDF]

				H. W. Tedford and G. W. Zamponi Direct G Protein Modulation of Cav2 Calcium Channels Pharmacol. Rev., December 1, 2006; 58(4): 837 - 862. [Abstract] [Full Text] [PDF]