The Erythropoietin Receptor: Dimerization, Activation, and Tumorigenesis
- *Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142; † Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; ‡ Division of Hematology-Oncology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
This extract was created in the absence of an abstract.
Excerpt
Blood cells continuously originate from low numbers of self-renewing pluripotent stem cells that generate progenitor cells committed to one or a few hematopoietic lineages. Control of these differentiation pathways is determined, in part, through specific growth factors binding to their cognate receptor(s) (Metcalf 1989). Abrogation or alteration of this control network may lead to the development of leukemia.
Erythropoietin (EPO) is a serum glycoprotein hormone required for the survival, proliferation, and differentiation of committed erythroid progenitor cells (Krantz 1991). We isolated by expression cloning the murine erythropoietin receptor (EPO-R) cDNA (D'Andrea et al. 1989b); it has sequence homology with other cytokine receptors (D'Andrea et al. 1989a). Conserved structural features of the cytokine receptor superfamily include four similarly spaced exoplasmic cysteine residues, as well as a motif, WSXWS, located in the exoplasmic domain close to the membrane-spanning region (Cosman et al. 1990). The EPO-R and other members of the cytokine receptor...
