Regulation of RGS3 and RGS10 palmitoylation by GnRH

Cecilia Castro-FERNÁNDEZ, J. O. Ann Janovick, Shaun P. Brothers, Rory A. Fisher, H. J.I. Tae, P. Michael Conn

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30 Scopus citations

Abstract

Regulators of G protein signaling (RGS) play a pivotal role in cellular signal transduction. RGS3 or RGS10 were overexpressed in GGH3 cells [GH3 cells stably expressing the GnRH receptor (GnRHR)]. Responsiveness to a GnRH agonist was assessed because RGS proteins attenuate production of inositol phosphates (IP) and/or cAMP, molecules believed to be involved in GnRH signaling. In addition, site-directed mutagenesis of a potentially palmitoylated Cys60 residue of RGS10 was used to assess the significance of this site. We observed maximum inhibition of GnRH-stimulated IP responses by RGS3 and by the conserved domain of RGS10 at both 48 and 72 h after transfection, indicating their involvement in Gqα mediated signaling. Significantly diminished cAMP production was observed at all times when cells over-expressed the conserved domain of RGS10; no effect was observed with RGS3 on Gsα-mediated signaling. Palmitic acid incorporation into RGS3 was dependent on agonist occupancy of GnRHR, whereas palmitoylation of RGS10 was constitutive. Mutation of the conserved Cys60 residue of RGS10 obviated its negative regulatory action on GnRH-stimulated responses, indicating that this site is crucial for its activity on this system. This study is the first demonstration of a role for palmitoylation of this conserved Cys60 in mammalian G protein signaling.

Original languageEnglish (US)
Pages (from-to)1310-1317
Number of pages8
JournalEndocrinology
Volume143
Issue number4
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology

Cite this

Castro-FERNÁNDEZ, C., Ann Janovick, J. O., Brothers, S. P., Fisher, R. A., Tae, H. J. I., & Michael Conn, P. (2002). Regulation of RGS3 and RGS10 palmitoylation by GnRH. Endocrinology, 143(4), 1310-1317. https://doi.org/10.1210/endo.143.4.8713