Activating mutations of Gs protein in monostotic fibrous lesions of bone
Activating mutations of Gs protein in monostotic fibrous lesions of bone
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DOI：
10.1002/jor.1100140221
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发表时间：
1996-03-01
影响因子：
2.8
通讯作者：
Wolfe, HJ
中科院分区：
文献类型：
--
作者：
Alman, BA;Greel, DA;Wolfe, HJ
异源三聚体信号转导器 Gs α 链的激活突变会破坏 α 链固有的鸟苷三磷酸酶活性，刺激腺苷酸环化酶，并可导致独立的细胞增殖。这种突变在许多内分泌疾病中被发现，包括麦库尼-奥尔布赖特综合征，这是内分泌病、咖啡牛奶斑和多骨性纤维异常增殖症的三联征。该综合征中的突变是外显子 8 中的错义点突变，导致 201 位精氨酸被组氨酸或半胱氨酸取代。单核性纤维发育不良是一种非遗传性孤立性骨病变。其他与纤维异常增殖症具有某些细胞学和临床相似性的孤立性骨病变是骨纤维异常增殖症和涉及骨的侵袭性纤维瘤病。研究人员对 4 例单性纤维异常增殖症、4 例累及骨的侵袭性纤维瘤病和 1 例骨纤维异常增殖症进行了研究，以确定 Gs α 链的外显子 8 中是否存在突变。所有纤维异常增生中均存在错义突变。其他纤维病变和未受累组织不包含突变。 Gs 的体细胞激活突变将纤维性发育不良与其他病变区分开来，并可能导致局部增殖和生长因子表达失控。
Activating mutations of the alpha chain of the heterotrimeric signal transducer Gs disrupt the inherent guanosine triphosphatase activity of the alpha chain, stimulate adenylyl cyclase, and can result in independent cell proliferation. Such mutations are identified in a number of endocrine disorders, including McCune-Albright syndrome, which is a triad of endocrinopathy, cafe au lait spots, and polyostotic fibrous dysplasia. The mutation in this syndrome is a missense point mutation in exon 8 that results in the substitution of either histidine or cysteine for arginine at position 201. Monostotic fibrous dysplasia is a nonhereditary isolated bone lesion. Other isolated bone lesions that share some cytologic and clinical similarities to fibrous dysplasia are osteofibrous dysplasia and aggressive fibromatosis involving bone. Four cases of monostotic fibrous dysplasia, four cases of aggressive fibromatosis involving bone, and one case of osteofibrous dysplasia were studied to determine if a mutation was present in exon 8 of the alpha chain of Gs. A missense mutation was present in all of the fibrous dysplasias. The other fibrous lesions and uninvolved tissue did not contain a mutation. Somatic activating mutations of Gs differentiate fibrous dysplasia from the other lesions and may be responsible for the loss of control of local proliferation and growth factor expression.