Filipek A, Soderling T R
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
Mol Cell Biochem. 1993 Mar 24;120(2):103-10. doi: 10.1007/BF00926082.
We have tested the hypothesis that activation of the insulin receptor tyrosine kinase is due to autophosphorylation of tyrosines 1146, 1150 and 1151 within a putative autoinhibitory domain. A synthetic peptide corresponding to residues 1134-1162, with tyrosines substituted by alanine or phenylalanine, of the insulin receptor beta subunit was tested for its inhibitory potency and specificity towards the tyrosine kinase activity. This synthetic peptide gave inhibition of the insulin receptor tyrosine kinase autophosphorylation and phosphorylation of the exogenous substrate poly(Glu, Tyr) with an approximate IC50 of 100 microM. Inhibition appeared to be independent of the concentrations of insulin or the substrate poly(Glu, Tyr) but was decreased by increasing concentrations of ATP. This same peptide also inhibited the EGF receptor tyrosine kinase but not a serine/threonine protein kinase. These results are consistent with the hypothesis that this autophosphorylation domain contains an autoinhibitory sequence.
胰岛素受体酪氨酸激酶的激活是由于假定的自抑制域内酪氨酸1146、1150和1151的自身磷酸化。我们测试了胰岛素受体β亚基中对应于残基1134 - 1162的合成肽（其中酪氨酸被丙氨酸或苯丙氨酸取代）对酪氨酸激酶活性的抑制效力和特异性。这种合成肽对胰岛素受体酪氨酸激酶自身磷酸化以及外源性底物聚（谷氨酸，酪氨酸）的磷酸化具有抑制作用，其近似IC50为100微摩尔。抑制作用似乎与胰岛素或底物聚（谷氨酸，酪氨酸）的浓度无关，但随着ATP浓度的增加而减弱。同样的这种肽也抑制表皮生长因子受体酪氨酸激酶，但不抑制丝氨酸/苏氨酸蛋白激酶。这些结果与该自身磷酸化域包含自抑制序列这一假说相符。
