Functional LCK is required for optimal CD28-mediated activation of the TEC family tyrosine kinase EMT/ITK

Spencer Gibson, Avery August, Donald Branch, Bo Dupont, Gordon B. Mills

    Research output: Contribution to journalArticlepeer-review

    59 Scopus citations

    Abstract

    Activation of CD28 on T lymphocytes initiates a cascade of intracellular events, which in concert with activation of the T cell receptor, culminates in production of cytokines and a functional immune response. One of the earliest biochemical changes observed following stimulation of CD28 is tyrosine phosphorylation. We have demonstrated that both the LCK and the EMT/ITK/TSK (EMT) intracellular tyrosine kinases are activated following cross-linking of CD28. Utilizing somatic cell mutants lacking LCK, we demonstrate that functional LCK is required for CD28-induced activation of EMT as evidenced by increased tyrosine phosphorylation and kinase activity. In support of a role for LCK in EMT activation, reconstitution of a LCK- negative Jurkat T cell line by transfection with normal LCK recreates CD28- mediated EMT activation. Furthermore, co-transfection of LCK and EMT into COS-7 cells showed that EMT becomes phosphorylated in the presence of LCK. In addition, increases in EMT association with CD28 were eliminated in a LCK- negative Jurkat cell line, but were restored following transfection of wild type LCK. The data are most compatible with a model in which LCK, either directly or indirectly, initiates EMT activation and association with CD28 following ligation of CD28.

    Original languageEnglish (US)
    Pages (from-to)7079-7083
    Number of pages5
    JournalJournal of Biological Chemistry
    Volume271
    Issue number12
    DOIs
    StatePublished - Mar 22 1996

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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