Huang C, Duncan J A, Gilman A G, Mumby S M
University of Texas Southwestern Medical Center, Department of Pharmacology, 5323 Harry Hines Boulevard, Dallas, TX 75235-9041, USA.
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):412-7. doi: 10.1073/pnas.96.2.412.
Heterotrimeric signal-transducing G proteins are organized at the inner surface of the plasma membrane, where they are positioned to interact with membrane-spanning receptors and appropriate effectors. G proteins are activated when they bind GTP and inactivated when they hydrolyze the nucleotide to GDP. However, the topological fate of activated G protein alpha subunits is disputed. One model declares that depalmitoylation of alpha, which accompanies activation by a receptor, promotes release of the protein into the cytoplasm. Our data suggest that activation of G protein alpha subunits causes them to concentrate in subdomains of the plasma membrane but not to be released from the membrane. Furthermore, alpha subunits remained bound to the membrane when they were activated with guanosine 5'-(3-O-thio)triphosphate and depalmitoylated with an acyl protein thioesterase. Limitation of alpha subunits to the plasma membrane obviously restricts their mobility and may contribute to the efficiency and specificity of signaling.
异源三聚体信号转导G蛋白定位于质膜内表面，在那里它们能够与跨膜受体及合适的效应器相互作用。G蛋白在结合GTP时被激活，在将核苷酸水解为GDP时失活。然而，活化的G蛋白α亚基的拓扑命运存在争议。一种模型认为，α亚基的去棕榈酰化伴随着受体激活，促使该蛋白释放到细胞质中。我们的数据表明，G蛋白α亚基的激活会使其聚集在质膜的亚结构域中，而不会从膜上释放。此外，当α亚基用鸟苷5'-(3-O-硫代)三磷酸激活并用酰基蛋白硫酯酶去棕榈酰化时，它们仍与膜结合。α亚基局限于质膜显然限制了它们的流动性，可能有助于信号传导的效率和特异性。
