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Eur J Immunol. 1997 Apr;27(4):834-41.

Itk, a T cell-specific tyrosine kinase, is required for CD2-mediated interleukin-2 promoter activation in the human T cell line Jurkat.

Author information

1
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.

Abstract

We investigated the functional role of Itk, a member of the cytoplasmic tyrosine kinase Tec family, in T cell activation. Stimulation of either CD2 or T cell receptor (TCR)/CD3 on Tcells by monoclonal antibody-mediated cross-linking induced tyrosine phosphorylation of Itk, which was maximal as early as 1 min after stimulation. The tyrosine kinase activity in the anti-Itk immunoprecipitate was significantly activated upon these stimulations. Interleukin-2 (IL-2) promoter activity stimulated by cross-linking of CD2, TCR/CD3, and CD28 with antibodies was significantly reduced by transient expression of an Itk mutant lacking the kinase activity. The reduction paralleled a decrease in tyrosine phosphorylation of endogenous wild-type Itk. Stimulation of CD2 or TCR/CD3 induced activation of the nuclear factor of activated T cells (NFAT), the binding site of which is included in the IL-2 gene promoter. The activation of NFAT was also impaired by expression of the Itk mutant. These results demonstrate that Itk plays a role in IL-2 production, indicating a critical involvement of Itk in the initial stage of T cell activation by mediating signals from the TCR/CD3 complex, CD2, and CD28.

PMID:
9130632
[Indexed for MEDLINE]

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