[Tyrosine kinases of the Src family, enzymes with multiple functions: from the growth of fibroblasts to the migration of epithelial cells].

S Roche
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引用次数: 0

Abstract

The tyrosine kinases of the Src family were first discovered due to their oncogenic properties. In untransformed fibroblasts, these kinases are activated as cells exists quiescence in response to some growth factors. Using microinjection to introduce catalytically inactive dominant-negative form of cSrc, as well as an antibody that neutralizes cSrc, Fyn and cYes, we have shown that Src kinases are required for DNA synthesis induced by most growth factors (PDGF, EGF, CSF-1, insulin, IGF-1). A functional link between Src kinases and the expression of the transcription factor c-Myc was also shown. In addition to cell growth promotion, some factors induce epithelial cell scattering and this also requires cSrc and cYes activities. However, in contrast to mitogenesis, they do not need novel gene expression for signalling but rather may act by phosphorylating components that regulate the cytoskeleton. Finally, increased Src kinase activities were found in several human carcinomas and we propose that these enzymes are involved in cell invasion.

[Src家族酪氨酸激酶,具有多种功能的酶:从成纤维细胞的生长到上皮细胞的迁移]。
Src家族的酪氨酸激酶是由于其致癌特性而首次被发现的。在未转化的成纤维细胞中,这些激酶在细胞对某些生长因子的反应中处于静止状态时被激活。通过微量注射引入催化失活的显性阴性cSrc,以及中和cSrc, Fyn和cYes的抗体,我们已经证明Src激酶是大多数生长因子(PDGF, EGF, CSF-1,胰岛素,IGF-1)诱导的DNA合成所必需的。Src激酶和转录因子c-Myc表达之间的功能联系也被证实。除了促进细胞生长外,一些因子还会诱导上皮细胞散射,这也需要证监会和cYes的活性。然而,与有丝分裂相反,它们不需要新的基因表达来传递信号,而是可能通过磷酸化调节细胞骨架的成分来起作用。最后,在几种人类癌症中发现Src激酶活性增加,我们认为这些酶参与了细胞侵袭。
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