A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection

Recent data indicate that several members of the Tec family of protein tyro sine kinases function in antigen receptor signal transduction. Txk, a Tec f amily protein tyrosine kinase, is expressed in both immature and mature T c ells and in mast cells. By overexpressing Txk in T cells throughout develop ment, ne found that Txk specifically augments the phospholipase C (PLC)-gam ma 1-mediated calcium signal transduction pathway upon T cell antigen recep tor (-TCR) engagement. Although Txk is structurally different from inducibl e T cell kinase (Itk), another Tec family member expressed in T cells, expr ession of the Txk transgene could partially rescue defects in positive sele ction and signaling in itk(-/-) mice. Conversely, in the itk(+/+) (wild-typ e) background, overexpression of Txk inhibited positive selection of TCR tr ansgenic thymocytes, presumably due to induction of cell death. These resul ts 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 a nalogous functions.