Nuclear Signalling Laboratory, Division for Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, P.O. Box 334, A.C.T. 2601, Canberra City, Australia.
Amino Acids. 1995 Jun;9(2):93-109. doi: 10.1007/BF00805831.
Lateral diffusion of membrane-integral receptors within the plane of the membrane has been postulated to be mechanistically important for signal transduction. Direct measurement of polypeptide hormone receptor lateral mobility using fluorescence photobleaching recovery techniques indicates that tyrosine kinase receptors are largely immobile at physiological temperatures. This is presumably due to their signal transduction mechanism which requires intermolecular autophosphorylation through receptor dimerization and thus immobilization for activation. In contrast, G-protein coupled receptors must interact with other membrane components to effect signal transduction, and consistent with this, the phospholipase C-activating vasopressin V1- and adenylate cyclase activating V2-receptors are highly laterally mobile at 37°C. Modulation of the V2-receptor mobile fraction (f) has demonstrated a direct correlation between f and receptor-agonist-dependent maximal cAMP productionin vivo at 37°C. This indicates that f is a key parameter in hormone signal transduction especially at physiological hormone concentrations, consistent with mobile receptors being required to effect V2-agonist-dependent activation of G-proteins. Measurements using a V2-specific antagonist show that antagonist-occupied receptors are highly mobile at 37°C, indicating that receptor immobilization is not the basis of antagonism. In contrast to agonist-occupied receptor however, antagonistoccupied receptors are not immobilized prior to endocytosis and down-regulation. Receptors may thus be freely mobile in the absence of agonistic ligand; stimulation by hormone agonist results in receptor association with other proteins, probably including cytoskeletal components, and immobilization. Receptor immobilization may be one of the important steps of desensitization subsequent to agonistic stimulation, through terminating receptor lateral movement which is instrumental in generating and amplifying the initial stimulatory signal within the plane of the membrane.
膜整合受体在膜平面内的侧向扩散被认为在信号转导中具有机械重要性。使用荧光漂白恢复技术直接测量多肽激素受体的侧向流动性表明，酪氨酸激酶受体在生理温度下基本处于不可移动状态。这可能是由于其信号转导机制需要通过受体二聚化进行分子间自磷酸化，从而固定化以激活。相比之下，G 蛋白偶联受体必须与其他膜成分相互作用才能进行信号转导，因此与这种情况一致，磷脂酶 C 激活的血管加压素 V1 和腺苷酸环化酶激活的 V2 受体在 37°C 时具有很高的侧向流动性。V2 受体可动分数 (f) 的调制表明，f 与体内 37°C 时受体-激动剂依赖性最大 cAMP 产生之间存在直接相关性。这表明 f 是激素信号转导的关键参数，特别是在生理激素浓度下，与移动受体能够影响 G 蛋白的 V2-激动剂依赖性激活一致。使用 V2 特异性拮抗剂的测量表明，在 37°C 时，被拮抗剂占据的受体具有很高的流动性，这表明受体固定化不是拮抗作用的基础。然而，与激动剂占据的受体不同，被拮抗剂占据的受体在胞吞作用和下调之前不会固定化。因此，受体在没有激动性配体的情况下可能是自由可移动的；激素激动剂的刺激导致受体与其他蛋白质（可能包括细胞骨架成分）的关联和固定化。受体固定化可能是激动刺激后脱敏的重要步骤之一，通过终止受体的侧向运动来终止，这种运动对于在膜平面内产生和放大初始刺激信号是至关重要的。
Zotero 插件