Agonist regulation of cellular G protein levels and distribution: mechanisms and functional implications.
Exposure of cells to agonists of receptors linked to G proteins can result in downregulation of cellular levels or redistribution of G proteins from membranes to the cytosol. Agonist-induced reductions in G protein levels have been observed for members of each of the Gs, Gi and Gq families of G proteins, are likely to be dependent upon the level of receptor expression, and are generally restricted to the G protein(s) with which the receptor interacts. The mechanisms responsible, reviewed here by Graeme Milligan, vary with cell type and include both second messenger-dependent and -independent enhanced protein degradation. Agonist-induced reduction in cellular G protein levels can provide one mechanism for the development of sustained heterologous desensitization.
Milligan
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Department of Biochemistry, University of Glasgow, UK.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*
D011956:Receptors, Cell Surface; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins