J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/03/1055/10 $2.00
Volume 185, Number 6, March 17, 1997 1055-1064

RAFTK, a Novel Member of the Focal Adhesion Kinase Family, Is Phosphorylated and Associates with Signaling Molecules upon Activation of Mature T Lymphocytes

By Ramesh K. Ganju,^* William C. Hatch,^* Hava Avraham,^* Mel A. Ona,^* Brian Druker, Shalom Avraham,^* and Jerome E. Groopman^*

From the ^* Divisions of Experimental Medicine and Hematology/Oncology, Beth Israel Deaconess Medical Center,  West Campus, Harvard Institutes of Medicine, Harvard Medical School, Boston, Massachusetts 02215; and the  Division of Hematology/Oncology, Oregon Health Sciences Center, Portland, Oregon 97201

The related adhesion focal tyrosine kinase (RAFTK), a recently discovered member of the focal adhesion kinase family, has previously been reported to participate in signal transduction in neuronal cells, megakaryocytes, and B lymphocytes. We have found that RAFTK is constitutively expressed in human T cells and is rapidly phosphorylated upon the activation 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. This association was mediated through the SH2 domains of Fyn and Grb2. RAFTK 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-mediated stimulation was reduced by the pretreatment of cells with cytochalasin D, suggesting the role of the cytoskeleton in this process. These observations indicate that RAFTK participates in T cell receptor signaling and may act to link signals from the cell surface to the cytoskeleton and thereby affect the host immune response.

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