Ala-->Gly mutation in the putative catalytic loop confers temperature sensitivity on Ros, insulin receptor, and insulin-like growth factor I receptor protein-tyrosine kinases.
Ala-->Gly mutation in the putative catalytic loop confers temperature sensitivity on Ros, insulin receptor, and insulin-like growth factor I receptor protein-tyrosine kinases.
复制标题
假定催化环中的 Ala-->Gly 突变赋予 Ros、胰岛素受体和胰岛素样生长因子 I 受体蛋白酪氨酸激酶温度敏感性。
DOI：
10.1073/pnas.91.1.321
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发表时间：
1994
影响因子：
11.1
通讯作者：
Wang,LH
中科院分区：
文献类型：
--
作者：
Chen,J;Hanafusa,T;Wang,LH
禽肉瘤病毒UR2癌基因ros编码受体蛋白酪氨酸激酶(PTK)，被鉴定为温度敏感突变。ROS激酶域中高度保守的RDLAARN基序中的Ala385-->；Gly变化映射是温度敏感表型的原因。根据已知的所有蛋白激酶的序列同源性和cAMP依赖的蛋白激酶的晶体结构，这个保守区域可能代表了PTK催化环。当将相同的突变引入人类胰岛素和胰岛素样生长因子I受体中时，使这些PTKs对生物功能和激酶活性的温度敏感。我们的结果支持这个高度保守的序列在PTKs中可能的催化作用。由于其高度保守的性质，我们预测相同的突变可能会赋予其他PTK温度敏感性。
Temperature-sensitive mutations in the avian sarcoma virus UR2 oncogene ros, encoding a receptor protein-tyrosine kinase (PTK), were identified. The Ala385-->Gly change mapping within the highly conserved RDLAARN motif in the Ros kinase domain was responsible for the temperature-sensitive phenotype. Based on the sequence homology of all known protein kinases and the crystalline structure of the cAMP-dependent protein kinase, this conserved region probably represents the PTK catalytic loop. The same mutation when introduced into the human insulin and insulin-like growth factor I receptors made these PTKs temperature sensitive in both biological function and kinase activity. Our results support the presumed catalytic role of this highly conserved sequence in PTKs. Due to its highly conserved nature, we predict that the same mutation would probably confer temperature sensitivity on other PTKs.