title: Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site.
abstract: Applying a homology search method previously described, we identified a sequence in the extracellular dimerization site of the erythropoietin receptor, distant from the hormone binding site. A peptide identical to that sequence was synthesized. Remarkably, it activated receptor signaling in the absence of erythropoietin. Neither the peptide nor the hormone altered the affinity of the other for the receptor; thus, the peptide does not bind to the hormone binding site. The combined activation of signal transduction by hormone and peptide was strongly synergistic. In mice, the peptide acted like the hormone, protecting against the decrease in hematocrit caused by carboplatin.
authors.affiliation: Receptron, Inc., 835 Maude Avenue, Mountain View, CA 94043, USA. tnaranda@receptron.com
authors.forename: T
authors.initials: T
authors.lastname: Naranda
authors.forename: K
authors.initials: K
authors.lastname: Wong
authors.forename: R I
authors.initials: RI
authors.lastname: Kaufman
authors.forename: A
authors.initials: A
authors.lastname: Goldstein
authors.forename: L
authors.initials: L
authors.lastname: Olsson
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017467:Receptors, Erythropoietin / Q000819:agonists* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010455:Peptides; D017467:Receptors, Erythropoietin