Abstract

The salient features of this proposal are: The study of those structural features of human erythropoietin that may be directly involved with its biological activity on hemopoietic precursor cells; the study of the primary structure of the active site; the determination of oligosaccharide side chain structure; the isolation and characterization of specific cellular receptors for erythropoietin from cells infected with the anemia strain of the Friend virus; the extension of receptor studies to normal mouse cells and to apply the methods developed for that purpose to the study of human cellular receptors. Once isolated the erythropoietin receptor will be cloned and the gene for the receptor used to test a hypothesis regarding erythroid cell differentiation. Mouse erythropoietin will also be cloned and the DNA used for the study of the regulation of expression of the erythropoietin gene as well as for the study of erythropoietin biogenesis and secretion. Another aim is to develop a solid-phase radioimmunoassay using monoclonal anti-epo with the intention of improving the sensitivity of analyis by an order of magnitude. The same monoclonal anti-epo will be used as the basis for an improved immunoaffinity purification method.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL021676-16
Application #
3485742
Study Section
Special Emphasis Panel (NSS)
Project Start
1985-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
16
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Kung, C; Fan, L; Goldwasser, E (2000) The role of tyrosine 15 in erythropoietin action. Arch Biochem Biophys 379:85-9
Mujais, S K; Beru, N; Pullman, T N et al. (1999) Erythropoietin is produced by tubular cells of the rat kidney. Cell Biochem Biophys 30:153-66
Haidar, M A; Loya, F; Yang, Y et al. (1997) Electron microscopic localization of lacZ expression in the proximal convoluted tubular cells of the kidney in transgenic mice carrying chimeric erythropoietin/lacZ gene constructs. J Struct Biol 118:220-5
Kung, C K; Goldwasser, E (1997) A probable conformational difference between recombinant and urinary erythropoietins. Proteins 28:94-8
Haidar, M A; Loya, F; Yang, Y et al. (1996) Differential expression of lacZ in the liver and kidney of transgenic mice carrying chimeric lacZ-erythropoietin gene constructs with or without its 1.2 kb 3'-flanking sequence. Nucleic Acids Res 24:3621-8
Goldwasser, E (1996) Erythropoietin: a somewhat personal history. Perspect Biol Med 40:18-32
Gupta, M; Goldwasser, E (1996) The role of the near upstream sequence in hypoxia-induced expression of the erythropoietin gene. Nucleic Acids Res 24:4768-74
Stage-Marroquin, B; Pech, N; Goldwasser, E (1996) Internal autocrine regulation by erythropoietin of erythroleukemic cell proliferation. Exp Hematol 24:1322-6
Cahan, C; Decker, M J; Arnold, J L et al. (1995) Erythropoietin levels with treatment of obstructive sleep apnea. J Appl Physiol 79:1278-85
Goldwasser, E; Alibali, P; Gardner, A (1995) Differential inhibition by iodonium compounds of induced erythropoietin expression. J Biol Chem 270:2628-9

Showing the most recent 10 out of 43 publications