Bjorge J D, Chan T O, Antczak M, Kung H J, Fujita D J
Department of Medical Biochemistry, University of Calgary, Canada.
Proc Natl Acad Sci U S A. 1990 May;87(10):3816-20. doi: 10.1073/pnas.87.10.3816.
We have shown that a type I phosphatidylinositol (PI) kinase activity is associated with the epidermal growth factor (EGF) receptor in a mouse fibroblast cell line expressing human EGF receptors (NRHER5) and that this activity increases dramatically upon treatment of cells with physiologically relevant concentrations of EGF. EGF stimulated a time-dependent increase in EGF receptor-associated PI kinase activity measured in EGF receptor immunoprecipitates. Activation was detected 15 min after the addition of EGF, and it peaked between 1 and 2 hr. Activation of PI kinase was detected with EGF concentrations as low as 10 pM and maximal stimulation occurred at approximately 1 nM. Analysis of deacylated PI phosphate products, and inhibition of the PI kinase activity by nonionic detergent, indicated that the PI kinase described here was type I or PI 3' kinase. These results demonstrate the regulation of a type I PI kinase by EGF and suggest a potential role in the EGF receptor signal transduction pathway.
我们已经证明,在表达人表皮生长因子(EGF)受体的小鼠成纤维细胞系(NRHER5)中,I型磷脂酰肌醇(PI)激酶活性与EGF受体相关,并且在用生理相关浓度的EGF处理细胞后,这种活性会显著增加。EGF刺激了在EGF受体免疫沉淀物中测得的EGF受体相关PI激酶活性的时间依赖性增加。在添加EGF后15分钟检测到激活,并且在1至2小时之间达到峰值。用低至10 pM的EGF浓度即可检测到PI激酶的激活,最大刺激发生在约1 nM处。对脱酰基PI磷酸产物的分析以及非离子去污剂对PI激酶活性的抑制表明,此处描述的PI激酶为I型或PI 3'激酶。这些结果证明了EGF对I型PI激酶的调节作用,并提示其在EGF受体信号转导途径中的潜在作用。