Constitutive activation of the MAPK pathway mediates v-<i>fes</i>-induced mitogenesis in murine macrophages

作     者：Rovida, E Marra, F Baccarini, M Dello Sbarba, P 

作者机构：Univ Florence Dipartimento Patol & Oncol Sperimentali I-50134 Florence Italy Univ Florence Dept Internal Med I-50134 Florence Italy Univ Vienna Inst Microbiol & Genet A-1090 Vienna Austria 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第12期

页      面：3959-3963页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：细胞分裂/生理学 细胞系 融合蛋白质类 gag-onc/遗传学 融合蛋白质类 gag-onc/生理学 巨噬细胞集落刺激因子/药理学 巨噬细胞/细胞学 巨噬细胞/生理学 丝裂原活化蛋白激酶1/代谢 丝裂原活化蛋白激酶3 丝裂原激活蛋白激酶类/代谢 受体 巨噬细胞集落刺激因子/生理学 重组融合蛋白质类/代谢 信号传导 动物 小鼠 

摘      要：Fes is a nonreceptor tyrosine kinase expressed at the highest level in macrophages, We previously showed that the overexpression of c-fes in murine macrophages of the BAC-1.2F5 cell line renders these cells independent of macrophage colony-stimulating factor (MCSF) for survival and proliferation, although no direct relationship could be established between tyrosine-phosphorylated substrates of Fes- and MCSF receptor-dependent signaling and mitogenesis. In this study, we investigated whether the mitogen-activated protein kinase (MAPK) pathway is involved in the growth factor-independent growth of v-fes-overexpressing macrophages, We found a constitutively increased phosphorylation of extracellularly regulated kinase (ERK) in v-fes-overexpressing macrophages as compared with mock-infected cells. This finding was associated with activation of nitrogen/extracellular signal-regulated kinase (MEK) and with constitutive localization of ERK in the nucleus. Treatment of v-fes-overexpressing cells with the MEK-specific inhibitor PD98059 markedly reduced cell growth, hyperphosphorylation, and nuclear localization of ERK, indicating that the MAPK pathway mediates the mitogenic effect of v-fes. (C) 2000 by The American Society of Hematology.