Proceedings of the Korean Society of Applied Pharmacology (한국응용약물학회:학술대회논문집)

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Decreased Expression of Phospholipase C-$\beta$2 in Human Platelets with Impaired Function

  • Lee, Sang-Bong (Cell cycle and Signal Transduction Research Unit, Korea Research Institute of Bioscience and) ;
  • A. Koneti Rao (Sol Sherry Thrombosis Research Center and Department of Medicine, Temple University School of Medicine) ;
  • Lee, Kweon-Haeng (Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health) ;
  • Xu Yang (Sol Sherry Thrombosis Research Center and Department of Medicine, Temple University School of Medicine) ;
  • Bae, Yun-Soo (Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health)
  • Published : 1996.11.01
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Abstract

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate (IP$_3$), mobilization of intracellular Ca$\^$2+/, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation. A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, seven, out often known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC-${\gamma}$2 > PLC-${\beta}$2 > PLC-${\beta}$3 > PLC-${\beta}$l > PLC-${\gamma}$ > PLC-$\delta$1 > PLC-${\beta}$4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-${\beta}$2, whereas PLC-${\beta}$4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-${\beta}$2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.

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