Erythropoietin receptor activation by a ligand-induced conformation change
Erythropoietin receptor activation by a ligand-induced conformation change
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DOI：
10.1126/science.283.5404.990
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发表时间：
1999-02-12
期刊：
影响因子：
56.9
通讯作者：
Michnick, SW
中科院分区：
文献类型：
--
作者：
Remy, I;Wilson, IA;Michnick, SW
促红细胞生成素和其他细胞因子受体被认为是通过激素诱导的二聚化和与受体胞内结构域相关的JAK激酶的自磷酸化而激活的。通过体内蛋白质片段互补实验，研究人员获得了另一种机制的证据，即未配体的促红细胞生成素受体二聚体以阻止JAK2激活的构象存在，但随后又经历了配体诱导的构象变化，从而允许JAK2被激活。这些结果与晶体学证据一致，证明了促红细胞生成素受体的非配体和配体结合形式的不同二聚体构型。
Erythropoietin and other cytokine receptors are thought to be activated through hormone-induced dimerization and autophosphorylation of JAK kinases associated with the receptor intracellular domains, An in vivo protein fragment complementation assay was used to obtain evidence for an alternative mechanism in which unliganded erythropoietin receptor dimers exist in a conformation that prevents activation of JAK2 but then undergo a ligand-induced conformation change that allows JAK2 to be activated, These results are consistent with crystallographic evidence of distinct dimeric configurations for unliganded and ligand-bound forms of the erythropoietin receptor.