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Activation and association of Stat3 with Src in v-Src-transformed cell lines.

机译:v-Src转化细胞系中Stat3与Src的激活和关联。

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STAT proteins are a group of latent cytoplasmic transcription factors which function as signal transducers and activators of transcription. Stat1 and -2 were originally identified to function in interferon signaling, and Stat1 was also found to be activated by epidermal growth factor (EGF) and other cytokines. New members of the STAT gene family are identified. Among them, Stat3 has 52.5% amino acid sequence homology with Stat1 and is activated by platelet-derived growth factor (PDGF), colony-stimulating factor 1 (CSF-1), EGF, interleukin-6, and other cytokines. Treatment of cells with EGF activates Stat1 and Stat3, which become phosphorylated on tyrosine residues to form homo - or heterodimers and translocate into the nucleus, binding to the sis-inducible element (SIE) in the c-fos promoter. Somatic cell genetic analyses demonstrated that Jaks, a family of nontransmembrane protein tyrosine kinases, are required for the activation of Stat1 and Stat2 in interferon-treated cells. However, little is known about the activation of Stat3 by growth factors. Here we report that in all v-Src-transformed cell lines examined, Stat3 is constitutively activated to bind to DNA and the phosphorylation of tyrosine on Stat3 is enhanced by the induction of v-Src expression. We also report that Src is shown to be associated with Stat3 in vivo, as well as in vitro, and phosphorylates Stat3 in vitro. Stat3 is also activated by CSF-1, possibly through CSF-1 receptor-c Src association in NIH 3T3 cells overexpressing CSF-1 receptors. Together, the data suggest that Src is involved in activation of Stat3 in growth factor signal transduction.
机译:STAT蛋白是一组潜在的细胞质转录因子,起着信号转导和转录激活剂的作用。最初确定Stat1和-2在干扰素信号传导中起作用,并且还发现Stat1被表皮生长因子(EGF)和其他细胞因子激活。确定了STAT基因家族的新成员。其中,Stat3与Stat1具有52.5%的氨基酸序列同源性,并被血小板衍生生长因子(PDGF),集落刺激因子1(CSF-1),EGF,白介素6和其他细胞因子激活。用EGF处理细胞会激活Stat1和Stat3,后者在酪氨酸残基上被磷酸化,形成同型或异型二聚体并转移到细胞核中,与c-fos启动子中的sis诱导因子(SIE)结合。体细胞遗传学分析表明,Jaks是非跨膜蛋白酪氨酸激酶家族,在干扰素处理的细胞中激活Stat1和Stat2是必需的。然而,关于生长因子对Stat3的激活知之甚少。在这里,我们报告在检查的所有v-Src转化细胞系中,Stat3被组成性激活以结合到DNA,并且通过诱导v-Src表达增强Stat3上酪氨酸的磷酸化。我们还报告说,Src被证明与体内以及体外的Stat3相关,并在体外磷酸化Stat3。 Stat3也可以通过CSF-1激活,可能是通过过表达CSF-1受体的NIH 3T3细胞中的CSF-1受体-c Src缔合。总之,数据表明Src参与了生长因子信号转导中Stat3的激活。

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