14-3-3 Interacts with regulator of G protein signaling proteins and modulates their activity

Thomas Benzing, Michael B. Yaffe, Thierry Arnould, Lorenz Sellin, Bernhard Schermer, Birgit Schilling, Rainer Schreiber, Karl Kunzelmann, German G. Leparc, Emily Kim, Gerd Walz

Research output: Contribution to journalArticlepeer-review

Abstract

Regulator of G protein signaling (RGS) proteins function as GTPase-activating proteins (GAPs) that stimulate the inactivation of heterotrimeric G proteins. We have recently shown that RGS proteins may be regulated on a post-translational level (Benzing, T., Brandes, R., Sellin, L., Schermer, B., Lecker, S., Walz, G., and Kim, E. (1999) Nat. Med. 5, 913-918). However, mechanisms controlling the GAP activity of RGS proteins are poorly understood. Here we show that 14-3-3 proteins associate with RGS7 and RGS3. Binding of 14-3-3 is mediated by a conserved phosphoserine located in the Gα-interacting portion of the RGS domain; interaction with 14-3-3 inhibits the GAP activity of RGS7, depends upon phosphorylation of a conserved residue within the RGS domain, and results in inhibition of GAP function. Collectively, these data indicate that phosphorylation-dependent binding of 14-3-3 may act as molecular switch that controls the GAP activity keeping a substantial fraction of RGS proteins in a dormant state.

Original languageEnglish
Pages (from-to)28167-28172
Number of pages6
JournalJ Biol Chem
Volume275
Issue number36
DOIs
Publication statusPublished - 8 Sep 2000

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