The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling

Weizhang Zeng, Xin Xu, Serguei Popov, Suchetana Mukhopadhyay, Peter Chidiac, Joseph Swistok, Waleed Danho, Keith A. Yagaloff, Stewart L. Fisher, Elliott M. Ross, Shmuel Muallem, Thomas M. Wilkie

Research output: Contribution to journalArticle

218 Scopus citations

Abstract

Regulators of heterotrimeric G protein signaling (RGS) proteins are GTPase-activating proteins (GAPs) that accelerate GTP hydrolysis by G(q) and G(i) α subunits, thus attenuating signaling. Mechanisms that provide more precise regulatory specificity have been elusive. We report here that an N- terminal domain of RGS4 discriminated among receptor signaling complexes coupled via G(q). Accordingly, deletion of the N-terminal domain of RGS4 eliminated receptor selectivity and reduced potency by 104-fold. Receptor selectivity and potency of inhibition were partially restored when the RGS4 box was added together with an N-terminal peptide. In vitro reconstitution experiments also indicated that sequences flanking the RGS4 box were essential for high potency GAP activity. Thus, RGS4 regulates G(q) class signaling by the combined action of two domains: 1) the RGS box accelerates GTP hydrolysis by Gα(q) and 2) the N terminus conveys high affinity and receptor-selective inhibition. These activities are each required for receptor selectivity and high potency inhibition of receptor-coupled G(q) signaling.

Original languageEnglish (US)
Pages (from-to)34687-34690
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number52
DOIs
StatePublished - Dec 25 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling'. Together they form a unique fingerprint.

  • Cite this

    Zeng, W., Xu, X., Popov, S., Mukhopadhyay, S., Chidiac, P., Swistok, J., Danho, W., Yagaloff, K. A., Fisher, S. L., Ross, E. M., Muallem, S., & Wilkie, T. M. (1998). The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling. Journal of Biological Chemistry, 273(52), 34687-34690. https://doi.org/10.1074/jbc.273.52.34687