Regulation of expression of megakaryocyte and platelet proteoglycans

The existence of proteoglycans in hematopoietic cells has been recognized for many years. However, elucidation of the structure and function of these molecules has only begun to be explored in recent years. This paper reviews the current status of knowledge of the structure, function and metabolism of the serglycin proteoglycan in megakaryocytes and megakaryocytic tumor cells. We have identified complex metabolic patterns of the serglycin proteoglycan in terms of regulation of overall hydrodynamic size, glycosaminoglycan chain length and disaccharide composition, and processing of the core protein in control cells or in the presence of phorbol 12-myristate 13-acetate or dimethylsulfoxide. We are currently studying the regulation of synthesis of this protein by analysis of promoter constructs in megakaryocytic and non-megakaryocytic hematopoietic cells. We have also tentatively identified a second proteoglycan, betaglycan, which is known also as the Type III transforming growth factor beta receptor. We have identified this molecule in human erythroleukemia and CHRF 288-11 cells by the presence of characteristic core proteins between 92-120 kDa, by its ability to adhere to Octyl Sepharose and by detection of mRNA. We hope to apply studies of proteoglycan metabolism in these cells to understanding the development of alpha granules and membrane elements in megakaryocytes.