The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling: LCK is required for optimal activation of EMT.
Functional T lymphocyte activation requires concurrent stimulation of the TCR complex and an accessory molecule, most frequently CD28. We have previously demonstrated that the TEC family tyrosine kinase EMT/ITK/TSK (EMT) is activated following cross-linking of CD28. We demonstrate herein that cross-linking of the CD3 component of the TCR complex also leads to EMT activation as indicated by a rapid and transient increase in EMT tyrosine phosphorylation and kinase activity in anti-EMT immunoprecipitates. However, although concurrent cross-linking of the TCR and CD28 results in a marked increase in production of the T cell growth factor IL-2, it does not result in a significant alteration in the magnitude or duration of EMT activation. Somatic cell mutants of the Jurkat T cell line, which lack the SRC family kinase LCK (JCaM1.6), fail to produce IL-2 when stimulated through the TCR complex. EMT activation, as evidenced by increased EMT tyrosine phosphorylation and EMT-associated kinase activity, was also greatly reduced following stimulation of the TCR in the JCaM1.6 Jurkat T cell mutants that lack LCK. In support of a role for LCK in EMT activation, reconstitution of the LCK-negative Jurkat T cell line by enforced expression of LCK restored TCR-mediated EMT activation. Taken together, the data indicate that the EMT tyrosine kinase is activated following cross-linking of the TCR, a process in which LCK likely plays an important role.
Gibson
S
S
Molecular Oncology, Division of Medicine, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
August
A
A
Kawakami
Y
Y
Kawakami
T
T
Dupont
B
B
Mills
G B
GB
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000502:physiology; D003432:Cross-Linking Reagents; D004357:Drug Synergism; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D003432:Cross-Linking Reagents; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C080813:emt protein-tyrosine kinase; D019061:src-Family Kinases