Expression and tyrosine phosphorylation of Cbl regulates macrophage chemokinetic and chemotactic movement
Expression and tyrosine phosphorylation of Cbl regulates macrophage chemokinetic and chemotactic movement
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DOI：
10.1002/jcp.10236
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发表时间：
2003-05-01
影响因子：
5.6
通讯作者：
Berton, G
中科院分区：
文献类型：
--
作者：
Caveggion, E;Continolo, S;Berton, G
从hck（-/-）igr（-/-）小鼠分离的原代巨噬细胞显示改变的形态和F-肌动蛋白细胞骨架结构以及减少的迁移。佛波醇肉豆蔻基乙酸酯（PMA），一种蛋白激酶C激活剂，已被报道增加巨噬细胞扩散和癌细胞运动，拯救这些hck（-/-）fgr（-/-）缺陷的能力进行了测试。虽然PMA处理的野生型和hck（-/-）fgr（-/-）巨噬细胞表现出相似的扁平、扩散表型，但PMA不能挽救hck（-/-）fgr（-/-）巨噬细胞迁移缺陷。相反，PMA处理的野生型和hck（-/-）fgr（-/-）巨噬细胞在自发和趋化性迁移中均存在缺陷，并且两者中Cbl原癌蛋白的酪氨酸磷酸化均降低。此外，c-cbl（-/-）巨噬细胞表现出与hck（-/-）fgr（-/-）巨噬细胞相同的运动障碍，并且与野生型巨噬细胞相比具有相似的形态，具有更少的极化和更多的背褶。由于在c-cbl（-/-）巨噬细胞中Hck和Fgr的表达和活性没有降低，这些结果表明Cbl可能是Src家族激酶调节的巨噬细胞运动途径的重要下游介质。J.细胞。195：276-289，2003. (C)2003 Wiley-Liss，Inc.
Primary macrophages isolated from hck(-/-) igr(-/-) mice display altered morphology and F-actin cytoskeletal structures and reduced migration. The ability of phorbol myristyl acetate (PMA), a protein kinase C activator that has been reported to increase macrophage spreading and carcinoma cell motility, to rescue these hck(-/-) fgr(-/-) defects was tested. Although PMA-treated wild-type and hck(-/-) fgr(-/-) macrophages exhibited a similar flattened, spread phenotype, PMA did not rescue the hck(-/-) fgr(-/-) macrophage migration defect. Instead, both PMA-treated wild type and hck(-/-) fgr(-/-) macrophages were defective in spontaneous and chemotactic migration and tyrosine phosphorylation of the Cbl protooncoprotein was decreased in both. Moreover, c-cbl(-/-) macrophages displayed the same impairment of motility as hck(-/-) fgr(-/-) macrophages and a similar morphology with less polarization and more dorsal ruffling than wild-type macrophages. As Hck and Fgr expression and activity were not decreased in c-cbl(-/-) macrophages, these results suggest that Cbl is likely to be an important downstream mediator of the Src family kinase-regulated macrophage motility pathway. J. Cell. Physiol. 195: 276-289, 2003. (C) 2003 Wiley-Liss, Inc.