Role of Tec kinase in nuclear factor of activated T cells signaling

The Tec protein kinase family includes tk, Itk, Tee, RIk and Bmx, which are critically involved in signals mediated by various cytokines and antigen r eceptors, Btk mutations cause severe immunodeficiencies, with defective a c ell function, In T cells, Tec regulates cytokine production, However, the d ownstream targets of these Tec kinases are poorly defined. Here we report t hat overexpression of Tec in T cells can regulate gene transcription throug h the nuclear factor of activated T cells (NF-AT), Using different reporter gene constructs, we establish that Tec in transfected T cells dramatically induced NF-AT-dependent gene transcription, which was prevented by a domin ant-negative mutant of NF-AT or by the immunosuppressive drug cyclosporin A . Tec appears to regulate NF-AT nuclear import, In addition, Tec influences cytoplasmic free calcium increase, Taken together, bur results identify NF -AT as a major downstream target of Tec kinases that is critically involved in transcriptional gene regulation, These observations highlight signaling pathways regulated by Tec kinases and provide new pharmacological targets to regulate immune functions.