RAFTK, A NOVEL MEMBER OF THE FOCAL ADHESION KINASE FAMILY, IS PHOSPHORYLATED AND ASSOCIATES WITH SIGNALING MOLECULES UPON ACTIVATION OF MATURE T-LYMPHOCYTES

The related adhesion focal tyrosine kinase (RAFTK), a recently discove red member of the focal adhesion kinase family, has previously been re ported to participate in signal transduction in neuronal cells, megaka ryocytes, and B lymphocytes. We have found that RAFTK is constitutivel y expressed in human T cells and is rapidly phosphorylated upon the ac tivation of the T cell receptor (TCR). This activation also results in an increase in the autophosphorylation and kinase activity of RAFTK. After its stimulation, there was an increase in the association of the src cytoplasmic tyrosine kinase Fyn and the adapter protein Grb2. Thi s association was mediated through the SH2 domains of Fyn and Grb2. RA FTK also co-immunoprecipitates with the SH2 domain of Lck and with the cytoskeletal protein paxillin through its COOH-terminal proline-rich domain. The tyrosine phosphorylation of RAFTK after T cell receptor-me diated stimulation was reduced by the pretreatment of cells with cytoc halasin D, suggesting the role of the cytoskeleton in this process. Th ese observations indicate that RAFTK participates in T cell receptor s ignaling and may act to link signals from the cell surface to the cyto skeleton and thereby affect the host immune response.