REPLACEMENT OF INSULIN-RECEPTOR TYROSINE RESIDUES 1162 AND 1163 COMPROMISES INSULIN-STIMULATED KINASE-ACTIVITY AND UPTAKE OF 2-DEOXYGLUCOSE
REPLACEMENT OF INSULIN-RECEPTOR TYROSINE RESIDUES 1162 AND 1163 COMPROMISES INSULIN-STIMULATED KINASE-ACTIVITY AND UPTAKE OF 2-DEOXYGLUCOSE
复制标题
DOI：
10.1016/0092-8674(86)90786-5
复制
发表时间：
1986-06-06
期刊：
影响因子：
64.5
通讯作者：
RUTTER, WJ
中科院分区：
文献类型：
--
作者：
ELLIS, L;CLAUSER, E;RUTTER, WJ
胰岛素刺激β酪氨酸残基的自身磷酸化。胰岛素受体 (IR) 亚基；这种修饰的胰岛素非依赖性激酶在体外增加了对外源底物的活性。我们在此表明，用苯丙氨酸替换一个或两个双酪氨酸（残基 1162 和 1163）会导致体外胰岛素激活的自磷酸化和激酶活性显着降低或丧失。在体内，这些突变不仅导致胰岛素刺激的 IR 自磷酸化显着减少，而且还导致胰岛素激活的 2-脱氧葡萄糖摄取量相应减少。此外，截短的IR蛋白（缺少最后112个氨基酸）具有不稳定的β。亚基；该突变体在体外或体内没有激酶活性，并且不介导胰岛素刺激的 2-脱氧葡萄糖摄取。因此，IR 自磷酸化参与了 IR 活性的调节，其中酪氨酸 1162 和 163 是该调节的主要位点。
Insulin stimulates the autophosphorylation of tyrosine residues of the .beta. subunit of the insulin receptor (IR); this modified insulin-independent kinase has increased activity toward exogenous substrates in vitro. We show here that replacement of one or both of the twin tyrosines (residues 1162 and 1163) with phenylalanine results in a dramatic reduction in or loss of insulin-activated autophosphorylation and kinase activity in vitro. In vivo, these mutations not only result in a substantial decrease in insulin-stimulated IR autophosphorylation but also in a parallel decrease in the insulin-activated uptake of 2-deoxyglucose. Furthermore, a truncated IR protein (lacking the last 112 amino acids) has an unstable .beta. subunit; this mutant has no kinase activity in vitro or in vivo and does not mediate insulin-stimulated uptake of 2-deoxyglucose. IR autophosphorylation is thus implicated in the regulation of IR activities, with tyrosines 1162 and 163 as major sites of this regulation.