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 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.
Ganju
R K
RK
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Hatch
W C
WC
Avraham
H
H
Ona
M A
MA
Druker
B
B
Avraham
S
S
Groopman
J E
JE
D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000302:isolation & purification / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D051418:Focal Adhesion Kinase 2; D051380:GRB2 Adaptor Protein; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D051419:Paxillin; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051418:Focal Adhesion Kinase 2; D051076:Proto-Oncogene Proteins c-fyn; D002118:Calcium