Expression of GTPase-deficient Gialpha2 results in translocation of cytoplasmic RGS4 to the plasma membrane.
The members of a recently identified protein family termed regulators of G-protein signaling (RGS) act as GTPase-activating proteins for certain Galpha subunits in vitro, but their physiological effects in cells are uncertain in the face of similar biochemical activity and overlapping patterns of tissue expression. Consistent with its activity in in vitro GTPase-activating protein assays, RGS4 interacts efficiently with endogenous proteins of the Gi and Gq subclasses of Galpha subunits but not with G12alpha or Gsalpha. Unlike other RGS proteins such as RGS9, RGS-GAIP, and Sst2p, which have been reported to be largely membrane-associated, a majority of cellular RGS4 is found as a soluble protein in the cytoplasm. However, the expression of a GTPase-deficient Gialpha subunit (Gialpha2-Q204L) resulted in the translocation of both wild type RGS4 and a non-Gialpha-binding mutant (L159F) to the plasma membrane. These data suggest that RGS4 may be recruited to the plasma membrane indirectly by G-protein activation and that multiple RGS proteins within a given cell might be differentially localized to determine a physiologic response to a G-protein-linked stimulus.
Druey
K M
KM
Laboratory of Immunoregulation, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
Sullivan
B M
BM
Brown
D
D
Fischer
E R
ER
Watson
N
N
Blumer
K J
KJ
Gerfen
C R
CR
Scheschonka
A
A
Kehrl
J H
JH
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism; D020710:RGS Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014162:Transfection
D011506:Proteins; D011518:Proto-Oncogene Proteins; D020710:RGS Proteins; D012333:RNA, Messenger; C098799:RGS4 protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498017:Gnai2 protein, rat