Shc is a substrate of the rat intestinal epidermal growth factor receptor tyrosine kinase.
Shc is a substrate of the rat intestinal epidermal growth factor receptor tyrosine kinase.
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Shc 是大鼠肠表皮生长因子受体酪氨酸激酶的底物。
DOI：
10.1016/0016-5085(95)90751-3
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发表时间：
1995
期刊：
影响因子：
29.4
通讯作者：
Polk,DB
中科院分区：
文献类型：
--
作者：
Polk,DB
背景和目的表皮生长因子 (EGF) 已被证明可以诱导肠道增殖和成熟；然而，关于肠道 EGF 受体酪氨酸激酶底物的信息很少。本研究的目的是确定src同源胶原样蛋白(Shc)是否是肠道EGF受体的体内底物。方法10日龄大鼠接受EGF治疗或母乳喂养。在一些实验中，IEC-6 细胞用 EGF 处理。通过免疫检测研究肠道组织和细胞部分，以比较肠道蛋白的酪氨酸磷酸化状态和亚细胞定位。结果EGF使肠道蛋白的总酪氨酸磷酸化状态增加三倍。 EGF 受体和 Shc 的酪氨酸磷酸化被 EGF 迅速增加。 Grb2 与 Shc 的关联增加了四倍和五倍。 EGF处理后30秒内Shc和相关磷酸酪氨酰蛋白的质膜易位增加。结论Shc是体内肠道EGF受体的底物。 EGF 诱导的 Shc 与接头蛋白 Grb2 的结合可能对肠道中 p21r 分配途径的激活具有影响。 EGF 诱导的 Shc 与另外两种磷酸酪氨酰蛋白的膜关联表明 Shc 参与肠道 EGF 受体信号传导的其他方面。
Background & AimsEpidermal growth factor (EGF) has been shown to induce intestinal proliferation and maturation; however, little information is available regarding substrates of the intestinal EGF receptor tyrosine kinase. The purpose of this study was to determine if src homologous collagen-like protein (Shc) was an in vivo substrate of the intestinal EGF receptor.MethodsTen-day-old rats were treated with EGF or were breast-fed. In some experiments, IEC-6 cells were treated with EGF. Intestinal tissue and cell fractions were studied by immunodetection to compare the tyrosine phosphorylation state and the subcellular localization of intestinal proteins.ResultsThe total tyrosine phosphorylation state of intestinal proteins was increased threefold by EGF. Tyrosine phosphorylation of the EGF receptor and Shc were rapidly increased by EGF. The association of Grb2 with Shc increased fourfold and fivefold. Plasma membrane translocation of Shc and associated phosphotyrosyl proteins was increased within 30 seconds of EGF treatment.ConclusionsShc is a substrate of the intestinal EGF receptor in vivo. EGF-induced association of Shc with the adapter protein Grb2 may have implications for activation of the p21rassignaling pathway in the intestine. The EGF-induced membrane association of Shc with two other phosphotyrosyl proteins suggests involvement of Shc in additional aspects of EGF-receptor signaling in the intestine.