Erythropoietin Receptors Induced by Dimethyl Sulfoxide Exhibit Positive Cooperativity Associated with an Amplified Biologic Response

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 6; pp. 2535 - 2539
• Main Authors: Yonekura, Shuji, Chern, Yijuang, Donahue, Kelly A., Feldman, Laurie, Vanasse, Gary J., Sytkowski, Arthur J.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15-03-1991; National Acad Sciences
• Subjects: 550201 - Biochemistry- Tracer Techniques; Acute erythroblastic leukemia; Animals; BASIC BIOLOGICAL SCIENCES; BIOCHEMICAL REACTION KINETICS; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; Blotting, Northern; BODY FLUIDS; Butyrates; CELL DIFFERENTIATION; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell membranes; Cell physiology; Cells; COS cells; demethyl sulfoxide; Dimethyl Sulfoxide - pharmacology; DMSO; ERYTHROCYTES; Erythroid cells; ERYTHROPOIETIN; Erythropoietin - metabolism; Erythropoietin receptors; Fundamental and applied biological sciences. Psychology; HORMONES; ISOTOPE APPLICATIONS; KINETICS; Leukemia, Erythroblastic, Acute; Leukemia, Experimental; MATERIALS; MEMBRANE PROTEINS; MESSENGER-RNA; Mice; MITOGENS; Models, Biological; Molecular and cellular biology; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PEPTIDE HORMONES; Pretreatment; PROTEINS; RADIORECEPTOR ASSAY; REACTION KINETICS; RECEPTORS; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - genetics; Receptors, Erythropoietin; Recombinant Proteins - metabolism; RNA; RNA, Neoplasm - genetics; RNA, Neoplasm - isolation & purification; signal transduction; SULFOXIDES; TRACER TECHNIQUES; Erythroleukemia; Erythropoiesis; Erythropoietin; Red blood cell; Dissociation constant; Rauscher leukemia; Hill coefficient; Cell differentiation; Signal transduction; Membrane receptor; Messenger RNA; Scatchard plot; Mechanism of action
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.6.2535

Erythropoietin triggers the differentiation of erythrocyte progenitors by binding to receptors on their plasma membrane. We report here that pretreatment of erythropoietin-responsive murine erythroleukemia cells with chemical inducers resulted in a striking increase in erythropoietin-specific hemoglobinization. This amplification of the erythropoietin biologic response was accompanied by the induction of a new population of high-density receptors (≈20,000 per cell) exhibiting marked positive cooperativity. Erythropoietin binding to new receptors displayed a convex upward Scatchard plot and a Hill coefficient (nH) of 6.75. Measurement of erythropoietin receptor mRNA demonstrated an initial decrease in receptor transcript followed by an approximately 2- to 3-fold increase after 24-48 hr. This increase in receptor message does not appear to account for the magnitude of the receptor up-regulation by dimethyl sulfoxide. We propose that this positive cooperativity reflects the interaction (clustering) of receptors, presumably through the formation of homooligomers or heterooligomers, and that this receptor interaction may amplify the erythropoietin signal transduction pathway.