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
See Usage Policy.
Use this Persistent URL to link to this item: http://resolver.caltech.edu/CaltechAUTHORS:DRUjbc99
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.
|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|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||05 Feb 2007|
|Last Modified:||26 Dec 2012 09:31|
Repository Staff Only: item control page