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人胰岛素受体cDNA:激素激活跨膜信号传导的结构基础。

The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling.

作者信息

Ebina Y, Ellis L, Jarnagin K, Edery M, Graf L, Clauser E, Ou J H, Masiarz F, Kan Y W, Goldfine I D

出版信息

Cell. 1985 Apr;40(4):747-58. doi: 10.1016/0092-8674(85)90334-4.

DOI:10.1016/0092-8674(85)90334-4
PMID:2859121
Abstract

A cloned approximately 5 kb cDNA (human placenta) contains the coding sequences for the insulin receptor. The nucleotide sequence predicts a 1382 amino acid precursor. The alpha subunit comprises the N-terminal portion of the precursor and contains a striking cysteine-rich "cross-linking" domain. The beta-subunit (the C-terminal portion of the precursor) contains a transmembrane domain and, in the intracellular region, the elements of a tyrosine phosphokinase: an ATP-binding site and a possible tyrosine autophosphorylation site or sites. The overall structure is reminiscent of the EGF receptor; the cross-linking domain of the alpha subunit and several regions of the beta subunit exhibit sequence homology with the EGF receptor. The phosphokinase domain also exhibits homology with some oncogenic proteins that have tyrosine phosphokinase activity, in particular, a striking homology with v-ros. Southern blotting experiments suggest that the coding region spans more than 45 kb. The insulin receptor gene is located on chromosome 19.

摘要

一个克隆的约5kb cDNA(来自人胎盘)包含胰岛素受体的编码序列。核苷酸序列预测其前体为1382个氨基酸。α亚基构成前体的N端部分,并含有一个显著的富含半胱氨酸的“交联”结构域。β亚基(前体的C端部分)含有一个跨膜结构域,在细胞内区域含有酪氨酸磷酸激酶的元件:一个ATP结合位点和一个或多个可能的酪氨酸自磷酸化位点。整体结构让人联想到表皮生长因子(EGF)受体;α亚基的交联结构域和β亚基的几个区域与EGF受体表现出序列同源性。磷酸激酶结构域也与一些具有酪氨酸磷酸激酶活性的致癌蛋白表现出同源性,特别是与v-ros有显著的同源性。Southern印迹实验表明编码区域跨度超过45kb。胰岛素受体基因位于19号染色体上。

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