u-44069 and Blood-Platelet-Disorders

The phosphorylation responses of platelet proteins after platelet stimulation with agonists were studied in patients with clinical bleeding disorders and various types of impaired platelet functional responses. Impaired collagen-induced phosphorylation, particularly of the 47 kd substrate (P47) for protein kinase C, was observed in one patient whose platelet defect appears to be an impaired initial response to weak platelet agonists but whose platelet secretory mechanism is normal. Reduced phosphorylation of a 31 kd polypeptide was also observed. The phosphorylation defect in this patient differs from that seen in another patient in whom impaired P47 and myosin light chain phosphorylation was observed but whose functional defect may be more closely related to secretion. The results provide further evidence that phosphorylation of P47 may play a role in platelet activation mechanisms preceding secretion and that abnormalities of phosphorylation of both P47 and myosin light chain may be associated with platelet functional defects in some patients with bleeding disorders.

Topics: Adenosine Diphosphate; Blood Platelet Disorders; Blood Platelets; Blood Proteins; Collagen; Edetic Acid; Epinephrine; Erythrocyte Aggregation; Humans; Myosins; Phosphoproteins; Phosphorylation; Platelet Storage Pool Deficiency; Prostaglandin Endoperoxides, Synthetic; Thromboxane A2