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

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 Galpha-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.
Mesh Terms:
14-3-3 Proteins, Amino Acid Sequence, Binding Sites, Cell Line, GTP-Binding Proteins, GTPase-Activating Proteins, Humans, Kinetics, Molecular Sequence Data, Mutagenesis, Insertional, Mutagenesis, Site-Directed, Phosphorylation, Proteins, RGS Proteins, Recombinant Proteins, Repressor Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Staurosporine, Transfection, Tyrosine 3-Monooxygenase
J. Biol. Chem.
Date: Sep. 08, 2000
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