Plasma membranes appear to play a crucial role in the expression and delivery of hematopoietic growth factors. Human B-lymphocyte derived erythroid burst promoting activity (B-BPA) is one such hematopoietic growth factor which is expressed in both soluble and plasma-membrane bound forms. The reason for the existence of these two physical forms remains unclear. B-BPA is an erythroid specific growth regulator, purified by the principal investigator, whose precise mechanism of action remains unknown. This proposal is concerned with the biochemistry and cell biology of B-BPA, which we address by the following specific aims: A) We will purify B-BPA and determine its amino acid sequence. The sequence(s) and physicochemical properties of soluble and membrane-derived B-BPA will be compared in order to determine how these two forms may differ. B) We will clone and express the B-BPA gene in both bacterial and eukaryotic cells, and recombinant growth factor will be compared structurally and functionally with the natural hormone. C) We will investigate the temporal appearance of soluble and membrane-bound B-BPA, as well as the interaction of the growth factor with responsive target cells. We will proceed toward the identification of a specific B-BPA receptor on responsive target cells. These studies are relevant to our understanding of the developmental biology of erythropoiesis and, potentially, to clinical red cell disorders.

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Beth Israel Deaconess Medical Center
United States
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Feldman, L; Davis, K L; Feeley, D M et al. (1993) A sensitive new bioassay for erythroid colony-stimulating factor. Exp Hematol 21:1657-62
Feldman, L; Frazier, J G; Sytkowski, A J (1992) B-lymphocyte-derived burst-promoting activity is a pleiotropic erythroid colony-stimulating factor, E-CSF. Exp Hematol 20:1223-8
Feldman, L; Heinzerling, R; Hillam, R P et al. (1992) Four unique monoclonal antibodies to the putative receptor binding domain of erythropoietin inhibit the biological function of the hormone. Exp Hematol 20:64-8