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

J Biol Chem. 2000 Sep 8;275(36):28167-72. doi: 10.1074/jbc.M002905200.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Amino Acid Sequence
  • Binding Sites
  • Cell Line
  • GTP-Binding Proteins*
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Proteins / metabolism*
  • RGS Proteins / chemistry
  • RGS Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Repressor Proteins*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Staurosporine / pharmacology
  • Transfection
  • Tyrosine 3-Monooxygenase*


  • 14-3-3 Proteins
  • GTPase-Activating Proteins
  • Proteins
  • RGS Proteins
  • RGS3 protein, human
  • RGS7 protein, human
  • Recombinant Proteins
  • Repressor Proteins
  • Rgs3 protein, mouse
  • Rgs3 protein, rat
  • Rgs7 protein, mouse
  • Tyrosine 3-Monooxygenase
  • GTP-Binding Proteins
  • Staurosporine