Research Project
3486213
We intend to define the structure of the promotor/enhancer subdomains of the PF4 gene and determine the relevance for biologic activity of these regions as well as of any tissue specific factors that might be necessary for gene expression. We hope to examine the effects of Megakaryocyte Stimulatory Factor on the synthesis of PF4 as well as other alpha granule proteins and elucidate the intracellular pathway be which this mediator acts to enhance biosynthesis and/or genetic control of alpha granule proteins that are present within megakaryocytes. We also expect to purify an inhibitor of megakaryocytopoiesis from human platelets, isolate cDNAs which code for the human as well as the rat platelet inhibitor and determine the primary structures of these components. Subsequently, we shall attempt to show that this inhibitor alters the expected bone marrow megakaryocyte parameters as well as the numbers of circulating platelets, and that blocking the action of this protein by immunologic means induces an elevation of the platelet count.
