GTK, a Src-related tyrosine kinase, induces nerve growth factor-independent neurite outgrowth in PC12 cells through activation of the Rap1 pathway -: Relationship to Shb tyrosine phosphorylation and elevated levels of focal adhesion kinase

作     者：Annerén, C Reedquist, KA Bos, JL Welsh, M 

作者机构：Uppsala Univ Biomedicum Dept Med Cell Biol S-75123 Uppsala Sweden Univ Utrecht Physiol Chem Lab NL-3584 CG Utrecht Netherlands Univ Utrecht Ctr Biomed Genet NL-3584 CG Utrecht Netherlands 

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

年 卷 期：2000年第275卷第37期

页      面：29153-29161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：衔接蛋白质类 信号转导 载体蛋白质类/代谢 黏着斑激酶1 黏着斑蛋白酪氨酸激酶类 膜蛋白质类/代谢 肿瘤蛋白质类 神经生长因子/药理学 神经突/生理学 PC12细胞 磷酰化 蛋白激酶类/代谢 蛋白酪氨酸激酶类/生理学 原癌基因蛋白质类/代谢 原癌基因蛋白质c-crk 受体 trkA 酪氨酸/代谢 rap1GTP结合蛋白质类/生理学 src同源域 src族激酶类 动物 大鼠 

摘      要：The rat pheochromocytoma cell line PC12 is extensively used as a model for studies of neuronal cell differentiation. These cells develop a sympathetic neuronlike phenotype when cultured in the presence of nerve growth factor. The present study was performed in or der to assess the role of mouse GTK (previously named BSK/IYK), a cytoplasmic tyrosine kinase belonging to the Src family, for neurite outgrowth in PC12 cells. We report that PC12 cells stably overexpressing GTK exhibit a larger fraction of cells with neurites as compared with control cells, and this response is not accompanied by an increased ERK activity. Treatment of the cells with the MEK inhibitor PD98059 did not reduce the GTK-dependent increased in neurite outgrowth. GTK expression induces a nerve growth factor-independent Rap1 activation, probably through altered CrkII signaling. We observe increased CrkII complex formation with p130(Cas), focal adhesion kinase (FAK), and Shb in PC12-GTK cells. The expression of GTK also correlates with a markedly increased content of FAK, phosphorylation of the adaptor protein Shb, and an association between these two proteins. Transient transfection of GTK-over-expressing cells with RalGDS-RBD or Rap1GAP, inhibitors of the Rap1 pathway, reduces the GTK-dependent neurite outgrowth. These data suggest that GTK participates in a signaling pathway, perhaps involving Shb, FAK and Rap1, that induces neurite outgrowth in PC12 cells.