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Seminars in Oncology Volume 28, Supplement 8, April 2001, Pages 19-23 Evolving Issues in Oncology: What is the @@'Optimal@@' Hemoglobin Level? Part one The erythropoietin receptor This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Linda Mulcahy , 1 From Ortho Biotech Inc, Raritan, NJ, USA Available online 13 August 2004. Abstract Erythropoietin (EPO) is the primary regulator of erythropoiesis, and promotes the survival, proliferation, and differentiation of erythroid progenitor cells. The EPO receptor belongs to the same family of receptors as growth hormone, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, and some interleukins. In the erythropoietic process, EPO induces homodimerization of the EPO receptor, which is located on the surface of erythroid progenitor cells. Dimerization activates the receptor-associated Janus kinase 2 via transphosphorylation. Specific tyrosines in the intracellular portion of the receptor are phosphorylated and serve as a docking site for intracellular proteins, including one of the signal transducers and activators of transcription (STAT5). This results in activating various cascades of signal transduction. STAT5 enters the nucleus on phosphorylation, inducing the transcription of erythroid genes. Phosphatases dephosphorylate Janus kinase 2 and downregulate the EPO receptor. Erythropoietin receptor activation seems to exert its effect by inhibiting apoptosis rather than by affecting the commitment of erythroid lineage, although the mechanism by which this occurs is as yet unclear. Anemia in cancer is associated with excessive production of cytokines that inhibit EPO synthesis, thereby interfering with the normal erythropoietic process, which leads to a reduction in red blood cells and the ability to oxygenate tissue. Article Outline • References Corresponding author. Address reprint requests to Linda Mulcahy, PhD, Ortho Biotech Inc, 700 US Hwy 202, Raritan, NJ 08869-0670. 1 Dr Mulcahy is an employee of Ortho Biotech Inc.