Milligan G
Department of Biochemistry, University of Glasgow, UK.
Trends Pharmacol Sci. 1993 Nov;14(11):413-8. doi: 10.1016/0165-6147(93)90064-Q.
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.
将细胞暴露于与G蛋白偶联的受体激动剂下，可能会导致细胞内G蛋白水平下调，或使G蛋白从细胞膜重新分布到细胞质中。对于G蛋白的Gs、Gi和Gq家族中的每一个成员，均已观察到激动剂诱导的G蛋白水平降低，这可能取决于受体表达水平，并且通常局限于与该受体相互作用的G蛋白。格雷姆·米利根在此处综述了其背后的机制，这些机制因细胞类型而异，包括依赖第二信使和不依赖第二信使的增强型蛋白质降解。激动剂诱导的细胞G蛋白水平降低可为持续性异源脱敏的发生提供一种机制。
