• Guerriero, Vincent (PI)

    Project: Research project

    Grant Details


    The long-term goal of this project is to gain a better understanding of the
    physiology and biochemistry of smooth muscle contraction. Regulation of
    smooth muscle contraction is by the Ca2+-calmodulin-dependent enzyme myosin
    light chain kinase (MLCK) that phosphorylates the regulatory light chain of
    myosin. Phosphorylation is a prerequisite for actin activation of myosin
    ATPase and contraction. It has been proposed that MLCK contains an
    inhibitory region that is regulated by calmodulin-binding. MLCK also
    contains a catalytic region and an actin-binding region. The function of
    the carboxy-terminus (approximately 24 kDa) is unknown, but preliminary
    evidence suggests that this portion is expressed independent of MLCK. The
    isolation of a partial cDNA for this enzyme makes it possible to use
    molecular biology techniques to further knowledge in this area by defining
    the relationship between the structure of these domains and function. This
    cDNA is 60% complete and includes the carboxy terminus, but the sequence of
    the amino terminal end of the molecule is unknown. The specific aims,
    proposed are: 1) Establish a bacterial system for the expression of active
    and Ca2+-calmodulin-dependent enzyme using the partial cDNA; 2) Define the
    domains contained within the partial cDNA using site-directed and deletion
    mutagenesis; 3) Determine the full-length sequence for MLCK by isolation of
    cDNA clones that extend the 5'-end of the partial cDNA; and 4) Characterize
    a new acidic protein (24 kDa) that has been isolated from smooth muscle and
    is thought to be identical with the carboxy-terminus of MLCK. MLCK is a key regulatory component in smooth muscle and a clear
    understanding of its mechanism is vital to our appreciation of normal
    smooth muscle function. This is a prerequisite for treatment of abnormal
    smooth muscle behavior; an important example is vascular smooth muscle.
    These studies will help in the design of pharmacological agents for the
    treatment of abnormal function.
    Effective start/end date4/1/903/31/97


    • National Institutes of Health: $107,314.00
    • National Institutes of Health: $118,019.00


    • Medicine(all)


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