CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE II

  • Soderling, Thomas, (PI)

    Project: Research project

    Project Details

    Description

    The objective of these studies is to delineate the molecular
    mechanisms by which brain Ca++/calmodulin(Cam)-dependent protein
    kinase II (CaM-kinase II) is regulated by binding of Ca /CaM and
    by autophosphorylation, both with the purified kinase and in intact
    cells and tissues. Long-term regulation of brain CaM-kinase II by
    covalent mechanisms (i.e., autophosphorylation) is of special
    interest because of the putative neuronal functions of this kinase.
    There is good evidence that presynaptically CaM-kinase II is
    intimately involved in Ca-dependent regulation of catecholamine
    biosynthesis and neurotransmitter exocytosis. CaM-kinase II
    comprises 50% of protein in the postsynaptic density of excitatory
    synapses and may be involved in long-term alterations of synaptic
    plasticity. Previous studies from this and other laboratories have led to the
    formulation of a model for the regulation of CaM-kinase II by
    binding of Ca/CaM and by autophosphorylation. This model will be
    tested using synthetic peptides, derived from the known sequence
    of the 50 kDa subunit of the brain CaM-kinase II, to characterize
    CaM-binding and substrate-directed inhibitory domains within the
    kinase sequence. Amino acids essential to these functions will be
    identified using altered peptide sequences. The effects of
    phosphorylation of consensus phosphorylation sites flanking these
    two domains will be assessed in terms of the function of these
    domains. These results will be utilized in the design of in vitro
    site-specific mutagenesis to test the functions of specific amino
    acids on the properties of the kinase. Lastly the ability of CaM-
    kinase II to undergo autophosphorylation and formation of Ca
    independent species in intact cells will be assessed in hippocampal
    brain slices and in cultured hippocampal cells and PC12 cells in
    response to Ca influx. These studies will further our
    understanding of the regulation and function of this
    multifunctional Ca++ -dependent kinase.
    StatusFinished
    Effective start/end date9/1/8911/30/11

    Funding

    • National Institutes of Health: $339,750.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $365,904.00
    • National Institutes of Health
    • National Institutes of Health: $368,900.00
    • National Institutes of Health: $339,750.00
    • National Institutes of Health
    • National Institutes of Health: $339,750.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $369,600.00
    • National Institutes of Health: $369,600.00
    • National Institutes of Health: $294,650.00
    • National Institutes of Health: $287,478.00
    • National Institutes of Health: $339,750.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health

    ASJC

    • Medicine(all)
    • Biochemistry, Genetics and Molecular Biology(all)

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