G protein defects in signal transduction.
G protein defects in signal transduction.
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G蛋白信号转导缺陷。
DOI：
10.1159/000023526
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Spiegel,AM
中科院分区：
文献类型：
--
作者：
Spiegel,AM
G蛋白将许多激素的受体偶联到调节第二信使新陈代谢的效应器上。一些内分泌疾病已经被证明是由G蛋白或G蛋白偶联受体的功能丧失或获得突变引起的。在假性甲状旁腺功能减退症Ia型(PHIa)中，存在广泛的激素抵抗(甲状旁腺激素、促甲状腺激素、促性腺激素)及其相关的异常体征，Albright遗传性骨营养不良。PHIb受试者外貌正常，对甲状旁腺素表现出肾脏抵抗。在麦古恩-奥尔布赖特综合征(MAS)中，受试者表现出自主内分泌功能亢进，并伴有骨纤维发育不良和皮肤色素沉着。已在PHIa中发现了G S-α基因的种系功能丧失突变，最近的证据表明G S-α基因是以组织特异性的方式父系印记的。G-S-α基因印迹异常可能是导致PHIb的原因。相比之下，MAS是由G S-α基因的功能获得错义突变引起的。
G proteins couple receptors for many hormones to effectors that regulate second messenger metabolism. Several endocrine disorders have been shown to be caused by either loss-or gain-of-function mutations in G proteins or G protein-coupled receptors. In pseudohypoparathyroidism type Ia (PHP Ia), there are generalized hormone resistance (parathyroid hormone [PTH], thyroid-stimulating hormone, gonadotropins) and associated abnormal physical features, Albright hereditary osteodystrophy. Subjects with PHP Ib are normal in appearance and show renal resistance to PTH. In McCune-Albright syndrome (MAS), subjects show autonomous endocrine hyperfunction associated with fibrous dysplasia of bone and skin hyperpigmentation. Germline loss-of-function mutations have been identified in the G s-α gene in PHP Ia, and recent evidence suggests that the G s-α gene is paternally imprinted in a tissue-specific manner. Abnormal imprinting of the G s-α gene may be the cause of PHP Ib. MAS, in contrast, is caused by gain-of-function missense mutations of the G s-α gene.