Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells

作     者：Ku, H Meier, KE 

作者机构：Med Univ S Carolina Dept Cell & Mol Pharmacol Charleston SC 29425 USA 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：2000年第275卷第15期

页      面：11333-11340页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

主　　题：细胞黏附/药物作用 细胞支架蛋白质类/代谢 丝裂原激活蛋白激酶类/生理学 桩蛋白 磷蛋白类/代谢 磷酰化 蛋白质酪氨酸磷酸酶类/生理学 蛋白酪氨酸激酶类/生理学 T淋巴细胞/代谢 十四酰佛波乙酯/药理学 胸腺瘤/代谢 胸腺瘤/病理学 肿瘤细胞 培养的 动物 小鼠 

摘      要：Intracellular signals can regulate cell adhesion via several mechanisms in a process referred to as inside-out signaling In phorbol ester-sensitive EL4 thymoma cells, phorbol-la-myristate 13-acetate (PMA) induces activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases and promotes cell adhesion. In this study, clonal EL4 cell lines with varying abilities to activate ERKs in response to PIMA were used to examine signaling events occurring downstream of ERK activation. Paxillin, a multifunctional docking protein involved in cell adhesion, was phosphorylated on serine/threonine residues in response to PMA treatment. This response was correlated with the extent and time course of ERK activation. PMA-induced phosphorylation of paxillin was inhibited by compounds that block the ERK activation pathway in EL4 cells, primary murine thymocytes, and primary murine splenocytes. Paxillin was phosphorylated in vitro by purified active ERK2. Two-dimensional electrophoresis revealed that PMA treatment generated a complex pattern of phosphorylated paxillin species in intact cells, some of which were generated by ERR-mediated phosphorylation in vitro. An ERK pathway inhibitor interfered with PMA-induced adhesion of sensitive EL4 cells to substrate. These findings describe a novel inside-out signaling pathway by which the ERK cascade may regulate events involved in adhesion.