Rhodopsin-family receptors associate with small G proteins to activate phospholipase D
Rhodopsin-family receptors associate with small G proteins to activate phospholipase D
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DOI：
10.1038/32937
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发表时间：
1998-03-26
期刊：
影响因子：
64.8
通讯作者：
Sealfon, SC
中科院分区：
文献类型：
--
作者：
Mitchell, R;McCulloch, D;Sealfon, SC
视紫红质家族的G蛋白偶联受体包含许多重要的神经和内分泌信号，这些受体激活异源三聚体G蛋白，并且在许多情况下还引起磷脂酶D的激活，磷脂酶D是一种可以由小G蛋白ARF和RhoA控制的酶（1-3）。在这里，我们表明，激活磷脂酶D，诱导许多，但不是所有的，Ca 2+动员G-蛋白偶联受体是敏感的ARF和RhoA的抑制剂。这种类型的受体与ARF或RhoA在暴露于激动剂时共免疫沉淀，并且GTP类似物对配体与受体结合的影响改变为小G蛋白的特征。这些受体在其第七跨膜结构域中包含氨基酸序列Asn-ProXXTyr，而能够激活磷脂酶D而不涉及ARF的受体包含序列AspProXXTyr。在促性腺激素释放激素受体中，后一序列突变为AsnProXXTyr赋予了对ARF抑制剂的敏感性，而5-HT 2A受体中5-羟色胺的相互突变降低了其对抑制剂的敏感性。因此，携带AsnProXXTyr基序的受体似乎与ARF和RhoA形成功能复合物。
G-protein-coupled receptors of the rhodopsin family transduce many important neural and endocrine signals, These receptors activate heterotrimeric G proteins and in many cases also cause activation of phospholipase D, an enzyme that can be controlled by the small G proteins ARF and RhoA(1-3). Here we show that the activation of phospholipase D that is induced by many, but not all, Ca2+-mobilizing G-protein-coupled receptors is sensitive to inhibitors of ARF and of RhoA. Receptors of this type were coimmunoprecipitated with ARF or RhoA on exposure to agonists, and the effects of GTP analogues on ligand binding to the receptor changed to a profile that is characteristic of small G proteins, These receptors contain the amino-acid sequence Asn-ProXXTyr in their seventh transmembrane domain, whereas receptors capable of activating phospholipase D without involving ARF contain the sequence AspProXXTyr. Mutation of this latter sequence to AsnProXXTyr in the gonadotropin-releasing hormone receptor conferred sensitivity to an inhibitor of ARF, and the reciprocal mutation in the 5-HT2A receptor for 5-hydroxy-tryptamine reduced its sensitivity to the inhibitor, Receptors carrying the AsnProXXTyr motif thus seem to form functional complexes with ARF and RhoA.