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.
Benzing
T
T
Department of Medicine, University Hospital of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany.
Yaffe
M B
MB
Arnould
T
T
Sellin
L
L
Schermer
B
B
Schilling
B
B
Schreiber
R
R
Kunzelmann
K
K
Leparc
G G
GG
Kim
E
E
Walz
G
G
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D019204:GTP-Binding Proteins; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D020710:RGS Proteins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase
D048948:14-3-3 Proteins; D020690:GTPase-Activating Proteins; D011506:Proteins; D020710:RGS Proteins; C485898:RGS3 protein, human; C492039:RGS7 protein, human; D011994:Recombinant Proteins; D012097:Repressor Proteins; C415085:Rgs3 protein, mouse; C437714:Rgs3 protein, rat; C492038:Rgs7 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D019204:GTP-Binding Proteins; D019311:Staurosporine