Sommers C L, Rabin R L, Grinberg A, Tsay H C, Farber J, Love P E
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Exp Med. 1999 Nov 15;190(10):1427-38. doi: 10.1084/jem.190.10.1427.
Recent data indicate that several members of the Tec family of protein tyrosine kinases function in antigen receptor signal transduction. Txk, a Tec family protein tyrosine kinase, is expressed in both immature and mature T cells and in mast cells. By overexpressing Txk in T cells throughout development, we found that Txk specifically augments the phospholipase C (PLC)-gamma1-mediated calcium signal transduction pathway upon T cell antigen receptor (TCR) engagement. Although Txk is structurally different from inducible T cell kinase (Itk), another Tec family member expressed in T cells, expression of the Txk transgene could partially rescue defects in positive selection and signaling in itk(-)(/)(-) mice. Conversely, in the itk(+/+) (wild-type) background, overexpression of Txk inhibited positive selection of TCR transgenic thymocytes, presumably due to induction of cell death. These results identify a role for Txk in TCR signal transduction, T cell development, and selection and suggest that the Tec family kinases Itk and Txk perform analogous functions.
近期数据表明，蛋白酪氨酸激酶Tec家族的多个成员在抗原受体信号转导中发挥作用。Txk是一种Tec家族蛋白酪氨酸激酶，在未成熟和成熟T细胞以及肥大细胞中均有表达。通过在整个发育过程中在T细胞中过表达Txk，我们发现Txk在T细胞抗原受体（TCR）激活后特异性增强磷脂酶C（PLC）-γ1介导的钙信号转导途径。尽管Txk在结构上与诱导性T细胞激酶（Itk）不同，Itk是在T细胞中表达的另一个Tec家族成员，但Txk转基因的表达可以部分挽救itk(-)(/)(-)小鼠阳性选择和信号传导方面的缺陷。相反，在itk(+/+)（野生型）背景下，Txk的过表达抑制了TCR转基因胸腺细胞的阳性选择，这可能是由于诱导细胞死亡所致。这些结果确定了Txk在TCR信号转导、T细胞发育和选择中的作用，并表明Tec家族激酶Itk和Txk具有类似的功能。
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