Activation of Ca2+/calmodulin-dependent protein kinase (CaM-kinase) IV by CaM-kinase kinase in Jurkat T lymphocytes

In Kyung Park, Thomas R. Soderling

    Research output: Contribution to journalArticle

    104 Scopus citations

    Abstract

    Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV), a member of the CaM-kinase family involved in transcriptional regulation, is stimulated by Ca2+/CaM but also requires phosphorylation by a CaM-kinase kinase for full activation. In this study we investigated the physiological role of a CaM-kinase cascade in Jurkat T human lymphocytes through antigen receptor (CD3) signaling. Total and Ca2+-independent CaM-kinase IV activities were increased 8-14-fold by anti-CD3 antibody. This CD3-mediated activation involved phosphorylation since the immunoprecipitated CaM-kinase IV from stimulated Jurkat cells could be subsequently inactivated in vitro by protein phosphatase 2A. CaM-kinase IV immunoprecipitated from unstimulated Jurkat cells or CD3-negative mutant Jurkat cells could be activated in vitro 10-40-fold by CaM-kinase kinase purified from rat brain or thymus, whereas CaM-kinase IV from CDS-stimulated wild-type Jurkat cells was only activated to 2-3-fold by exogenous CaM-kinase kinase. CaM-kinase IV activation was triggered by Ca2+ acting through calmodulin since activation could also be elicited by ionomycin treatment, and CD3-mediated activation was blocked by the calmodulin antagonist calmidazolium. These data are consistent with a CaM-kinase cascade in which CaM-kinase IV is activated by a CaM-kinase kinase cascade triggered by elevated intracellular calcium in Jurkat cells.

    Original languageEnglish (US)
    Pages (from-to)30464-30469
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume270
    Issue number51
    DOIs
    StatePublished - Dec 22 1995

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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