The protein tyrosine p56^kk regulates thymocyte development independently of its interaction with CD4 and CD8 coreceptors

The lck gene encodes a lymphocyte-specific protein tyrosine kinase of the nonreceptor type that is implicated in signal transduction pathways emanating from the CD4 and CD8 coreceptors. Previous studies also support a role for p56^lck in regulating T cell receptor β gene rearrangements and, more generally, thymocyte development. Here we report that a mutant form of p56^lck, which is incapable of interacting with CD4 or CD8, behaves indistinguishably from association-competent p56^lck with respect to its ability to affect thymocyte maturation. The effects of p56^lck remained specific in that the closely related src-family kinase p59^hck was incapable of substituting for p56^lck in arresting β locus gene rearrangements. These data support the view that src-family kinases perform highly specialized and often nonoverlapping functions in hematopoietic cells, and that p56^lck acts independently of its association with CD4 and CD8 to regulate thymocyte development.