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Keeping the (Kinase) Party Going: SLP-76 and ITK Dance to the Beat

机译:保持(激酶)聚会的顺利进行:SLP-76和ITK跳动跳舞

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摘要

The Tec-family protein tyrosine kinase IL-2–inducible T cell kinase (ITK) mediates T cell activation, as does the adaptor protein SLP-76 (SH2-domain–containing leukocyte protein of 76 kD), which forms a complex with ITK and other intracellular signaling enzymes. One of these enzymes is phospholipase C–γ1 (PLC-γ1), which mediates T cell receptor (TCR)–stimulated intracellular calcium mobilization leading to the activation of transcription factors such as nuclear factor of activated T cells. The Src-family tyrosine kinase Lck and the Syk-family tyrosine kinase ζ chain–associated protein kinase of 70 kD (ZAP-70), together with ITK, are necessary for the phosphorylation of PLC-γ1 in response to TCR stimulation. ITK is thought to phosphorylate a specific tyrosine residue of PLC-γ1 that is required for its activation. The mechanism of activation of ITK appears to involve the interaction between SLP-76 and ITK, which not only initiates ITK activity but is also important to maintain the kinase activity of ITK. This suggests that SLP-76 acts as more than a neutral adaptor in mediating T cell activation; SLP-76 also directly influences the kinase activity of ITK, allowing ITK to phosphorylate PLC-γ1.
机译:Tec家族蛋白酪氨酸激酶IL-2诱导型T细胞激酶(ITK)介导T细胞活化,衔接子蛋白SLP-76(含SH2结构域的白细胞蛋白76 kD)也介导T细胞活化,该蛋白与ITK形成复合物和其他细胞内信号转导酶。这些酶之一是磷脂酶C-γ1(PLC-γ1),它介导T细胞受体(TCR)刺激的细胞内钙动员,从而导致转录因子(例如活化T细胞的核因子)的活化。 Src家族酪氨酸激酶Lck和Syk家族酪氨酸激酶ζ链相关蛋白激酶70 kD(ZAP-70)与ITK一起是响应TCR刺激而使PLC-γ1磷酸化所必需的。人们认为,ITK会活化PLC-γ1的特定酪氨酸残基。 ITK的激活机制似乎涉及SLP-76和ITK之间的相互作用,这不仅会启动ITK活性,而且对于维持ITK的激酶活性也很重要。这表明SLP-76在介导T细胞活化中起的作用不只是中性适配器。 SLP-76也直接影响ITK的激酶活性,从而使ITK磷酸化PLC-γ1。

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  • 期刊名称 other
  • 作者

    Qian Qi; Avery August;

  • 作者单位
  • 年(卷),期 -1(2007),396
  • 年度 -1
  • 页码 pe39
  • 总页数 7
  • 原文格式 PDF
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