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Amino-terminal cysteine residues of RGS16 are required for palmitoylation and modulation of G(i)- and G(q)-mediated signaling

Druey, Kirk M. and Ugur, Ozlem and Caron, Joan M. and Chen, Ching-Kang and Backlund, Peter S. and Jones, Teresa L. Z. (1999) Amino-terminal cysteine residues of RGS16 are required for palmitoylation and modulation of G(i)- and G(q)-mediated signaling. Journal of Biological Chemistry, 274 (26). pp. 18836-18842. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:DRUjbc99

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Abstract

RGS proteins (Regulators of G protein Signaling) are a recently discovered family of proteins that accelerate the GTPase activity of heterotrimeric G protein α subunits of the i, q, and 12 classes. The proteins share a homologous core domain but have divergent amino-terminal sequences that are the site of palmitoylation for RGS-GAIP and RGS4. We investigated the function of palmitoylation for RGS16, which shares conserved amino-terminal cysteines with RGS4 and RGS5. Mutation of cysteine residues at residues 2 and 12 blocked the incorporation of [3H]palmitate into RGS16 in metabolic labeling studies of transfected cells or into purified RGS proteins in a cell-free palmitoylation assay. The purified RGS16 proteins with the cysteine mutations were still able to act as GTPase-activating protein for Giα. Inhibition or a decrease in palmitoylation did not significantly change the amount of protein that was membrane-associated. However, palmitoylation-defective RGS16 mutants demonstrated impaired ability to inhibit both Gi- and Gq-linked signaling pathways when expressed in HEK293T cells. These findings suggest that the amino-terminal region of RGS16 may affect the affinity of these proteins for Gα subunits in vivo or that palmitoylation localizes the RGS protein in close proximity to Gα subunits on cellular membranes.


Item Type:Article
Additional Information:© 1999 by the American Society for Biochemistry and Molecular Biology. Received for publication, December 23, 1998, and in revised form, April 12, 1999. This work was supported by an American Cancer Society Grant ACSIN153M-150. We thank Dr. Yukiko Miura for assistance with the adenylyl cyclase assay and Dr. Paul K. Goldsmith for the AS antibody. 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.
Subject Keywords:GTPASE-ACTIVATING PROTEIN; PLASMA-MEMBRANE LOCALIZATION; ACTIVITY IN-VITRO; ALPHA-SUBUNITS; CORE DOMAIN; TRANSITION-STATE; GAIP; PHOSPHORYLATION; REGULATOR; RECEPTOR
Record Number:CaltechAUTHORS:DRUjbc99
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:DRUjbc99
Alternative URL:http://www.jbc.org/cgi/content/abstract/274/26/18836
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7352
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:05 Feb 2007
Last Modified:26 Dec 2012 09:31

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