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The interaction between IGF-I-dependent and other hormones-dependent signal pathways in cell growth and differentiation

细胞生长和分化中IGF-I依赖性和其他激素依赖性信号通路之间的相互作用

基本信息

批准号：
03660078
负责人：
TAKAHASHI Shin-ichiro
金额：
$ 1.28万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Studies were undertaken to determine the mechanism(s) by which thyroid stimulating hormone (TSH) and insulin-like growth factor-I (IGF-I) act synergistically to stimulate protein synthesis and DNA synthesis in FRTL-5 cells. The response of these cells to TSH and IGF-I greatly surpass the sum of the effects of the individual hormones when acting alone. Preincubation with IGF-I potentiates the effect of TSH on protein synthesis. On the contrary,after preincubation with TSH,FRTL-5 cells exhibited greatly increased response to the mitogenic activity of IGF-I.Furthermore,pretreatment of the cells for 24h with either TSH or other agents that elevate intracellular cAMP potentiated the IGF-I-dependent tyrosine phosphorylation (pp175 and pp95),and increased IGF-I-independent tyrosine phosphorylation(pp125, pp100 and pp80). These results suggest that a cAMP stimulus can be propagated through multiple pathways including enhancement of tyrosine phosphorylation. These phenomena were also observed in primary cultures of rat hepatocytes treated with cAMP-generating agents and insulin. The purification of pp175 from the lysates of FRTL-5 cells treated with Bt_2cAMP and IGF-I is in progress in our laboratory,using DEAE-ion exchange chromatography,anti-phosphotyrosine antibody conjugated Sepharose affinity chromatography,and SDS-polyacryl amide gel electrophoresis.

进行研究以确定促甲状腺激素（TSH）和胰岛素样生长因子-I（IGF-I）协同作用以刺激FRTL-5细胞中的蛋白质合成和DNA合成的机制。这些细胞对TSH和IGF-I的反应远远超过单独作用时单个激素的作用之和。IGF-I预孵育可增强TSH对蛋白质合成的影响。与此相反，在与TSH预孵育后，FRTL-5细胞表现出对IGF-I的促有丝分裂活性的反应大大增加。此外，用TSH或其他升高细胞内cAMP的试剂预处理细胞24小时，增强了IGF-I依赖的酪氨酸磷酸化（pp 175和pp 95），并增加了IGF-I非依赖的酪氨酸磷酸化（pp 125，pp 100和pp 80）。这些结果表明，cAMP刺激可以通过多种途径传播，包括增强酪氨酸磷酸化。在用cAMP生成剂和胰岛素处理的大鼠肝细胞的原代培养物中也观察到这些现象。本实验室用Bt_2cAMP和IGF-I处理FRTL-5细胞裂解液，经DEAE-离子交换层析、抗磷酸酪氨酸抗体偶联Sepharose亲和层析和SDS-聚丙烯酰胺凝胶电泳，对pp 175进行纯化。