Caldesmon is a calmodulin and actin binding protein which has been shown to decrease actin-activated myosin MgATPase activity. This inhibition can be reversed in the presence of calcium and calmodulin. It has been suggested that caldesmon may play a role in the regulation of actin-myosin interaction. Although the concentration of calcium may influence the ability of caldesmon to exert its effect, other evidence suggests that another regulatory mechanism may also be important. It has been shown that the inhibitory effect of caldesmon on actin-activated myosin MgATPase can be reduced following phosphorylation of caldesmon by a CaM-dependent protein kinase. Caldesmon also appears to be a substrate for protein kinase C. More recently, it was demonstrated that protein kinase C phosphorylates caldesmon when intact platelets are stimulated with phorbol esters. These observations suggest that phosphorylation of caldesmon may play a role in the cytoskeletal and/or contractile changes which occur in the platelet during activation. This project will examine the physiologic role of caldesmon in the intact platelet.
