| Abstract: |
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. |
| Keywords: |
signal transduction; drug potentiation; t lymphocyte; t-lymphocytes; metabolism; enzyme activation; enzymology; tumor cells, cultured; protein tyrosine kinase; phosphorylation; physiology; monoclonal antibody; drug synergism; t cell lymphoma; lymphoma, t-cell; immunology; antibodies, monoclonal; cell culture; receptors, antigen, t-cell; protein-tyrosine kinases; src-family kinases; lymphocyte antigen receptor; cd28 antigen; protein kinase lck; antigens, cd28; cross linking reagent; cross-linking reagents; lymphocyte specific protein tyrosine kinase p56(lck); humans; human; article; emt protein tyrosine kinase; emt protein-tyrosine kinase
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