Siliciano J D, Morrow T A, Desiderio S V
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11194-8. doi: 10.1073/pnas.89.23.11194.
T lymphocytes are activated by interactions with antigens, lymphokines, and cell adhesion molecules. Tyrosine phosphorylation has been implicated as important in signaling through each of these pathways, but except for p56lck, a member of the Src family that associates with CD4 and CD8, the protein-tyrosine kinases involved have not been defined. We describe here a tyrosine kinase gene that we have designated itk (for IL-2-inducible T-cell kinase). The itk gene specifies a 72-kDa protein-tyrosine kinase that is related to members of the Src family but lacks two features characteristic of Src kinases: an N-terminal myristoylation consensus sequence and a regulatory tyrosine residue near the C terminus. Analysis of mouse tissues and cell lines indicates that itk is specifically expressed in the T-cell lineage, suggesting that the tyrosine kinase encoded by itk functions in a signal transduction pathway unique to T lymphocytes. On addition of IL-2 to responsive T cells, itk RNA increases in parallel with that of IL-2R alpha, implicating itk in T-cell activation.
T淋巴细胞通过与抗原、淋巴因子和细胞粘附分子相互作用而被激活。酪氨酸磷酸化在这些信号传导途径中都被认为起着重要作用,但除了与CD4和CD8相关联的Src家族成员p56lck外,所涉及的蛋白酪氨酸激酶尚未明确。我们在此描述了一个酪氨酸激酶基因,我们将其命名为itk(IL-2诱导型T细胞激酶)。itk基因编码一种72 kDa的蛋白酪氨酸激酶,它与Src家族成员相关,但缺乏Src激酶的两个特征:N端肉豆蔻酰化共有序列和C端附近的一个调节性酪氨酸残基。对小鼠组织和细胞系的分析表明,itk在T细胞谱系中特异性表达,这表明itk编码的酪氨酸激酶在T淋巴细胞特有的信号转导途径中发挥作用。向反应性T细胞中添加IL-2后,itk RNA与IL-2Rα的RNA平行增加,这表明itk参与T细胞激活。