DIVERGENT INSULIN AND PLATELET-DERIVED GROWTH-FACTOR REGULATION OF FOCAL ADHESION KINASE (PP125(FAK)) TYROSINE PHOSPHORYLATION, AND REARRANGEMENT OF ACTIN STRESS FIBERS
DIVERGENT INSULIN AND PLATELET-DERIVED GROWTH-FACTOR REGULATION OF FOCAL ADHESION KINASE (PP125(FAK)) TYROSINE PHOSPHORYLATION, AND REARRANGEMENT OF ACTIN STRESS FIBERS
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DOI：
10.1074/jbc.270.17.10199
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发表时间：
1995-04-28
影响因子：
4.8
通讯作者：
PESSIN, JE
中科院分区：
文献类型：
--
作者：
KNIGHT, JB;YAMAUCHI, K;PESSIN, JE
胰岛素处理表达高水平人胰岛素受体的中国仓鼠卵巢细胞导致125 kDa粘着斑激酶（pp125（FAK））的酪氨酸去磷酸化。pp125（FAK）酪氨酸磷酸化的减少表明肌动蛋白应力纤维的细胞含量减少，这些变化与细胞生长的细胞外基质无关。pp125（FAK）酪氨酸磷酸化和肌动蛋白应激纤维的减少均以胰岛素浓度依赖性方式发生，在约0.3 nM时具有显著作用，在3 nM时具有最大作用。然而，在胰岛素的持续存在下，pp125（FAK）的酪氨酸磷酸化状态和肌动蛋白应力纤维含量的降低是暂时的。在胰岛素处理15分钟后观察到pp125（FAK）酪氨酸磷酸化的最大降低，60分钟时恢复到未刺激的对照水平。胰岛素处理15分钟后，肌动蛋白应激纤维含量最大程度减少，60分钟后完全恢复。与胰岛素相反，血小板衍生生长因子刺激增加了肌动蛋白应激纤维含量并增强了pp125（FAK）酪氨酸磷酸化，这些数据表明，胰岛素在诱导pp125（FAK）的酪氨酸去磷酸化和伴随的肌动蛋白应力纤维的重组，这是胰岛素和血小板衍生生长因子受体酪氨酸激酶之间的信号分歧的至少一个方面的基础的新的信号作用。
Insulin treatment of Chinese hamster ovary cells expressing high levels of the human insulin receptor resulted in the tyrosine dephosphorylation of the 125-kDa focal adhesion kinase (pp125(FAK)). The decrease in pp125(FAK) tyrosine phosphorylation paralleled a decrease in the cellular content of actin stress fibers, and these changes were independent of the extracellular matrix on which the cells were grown. The reduction in both pp125(FAK) tyrosine phosphorylation and actin stress fibers occurred in an insulin concentration-dependent manner, with significant effects at approximately 0.3 nM and a maximal effect at 3 nM. However, in the continuous presence of insulin, the decreases in the tyrosine phosphorylation state of pp125(FAK) and actin stress fiber content were transient, Maximal reduction of pp125(FAK) tyrosine phosphorylation was observed following 15 min of insulin treatment, with a return to unstimulated control levels by 60 min. Similarly, actin stress fiber content was maximally reduced by 15 min of insulin treatment and fully recovered by 60 min. In contrast to insulin, platelet-derived growth factor stimulation increased actin stress fiber content and enhanced pp125(FAK) tyrosine phosphorylation, These data demonstrate a novel signaling role for insulin in inducing the tyrosine dephosphorylation of pp125(FAK) and a concomitant reorganization of actin stress fibers, which underlies at least one aspect of signaling divergence between the insulin and platelet-derived growth factor receptor tyrosine kinases.