title: Activation of erythropoietin receptor through a novel extracellular binding site.
abstract: Activation of erythropoietin (EPO) receptor (EPOR) by a small peptide (ERP) was reported previously. ERP binds to a different receptor site than EPO, and binding of ERP does not change the dissociation constant and maximal binding for EPO binding to the receptor. The extracellular binding site for ERP is now characterized. The site is located in the membrane proximal, extracellular part of the receptor. ERP binds to a region on the EPOR that contains the same sequence as ERP. It is speculated that ERP binds to its identical sequence on EPOR, as ERP self-interacts. ERP is specific for EPOR and associates noncovalently with EPOR in a ratio 1:1. Peptide binding to the receptor results in receptor-mediated cellular proliferation, intracellular signaling, and erythroid colony-forming unit formation in bone marrow cells. The activity is comparable to that of EPO. Recognition of such receptor sites represents a new and important concept in receptor function.
authors.affiliation: Receptron, Inc., Mountain View, California 94043, USA.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Naranda
authors.forename: R Ilene
authors.initials: RI
authors.lastname: Kaufman
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wong
authors.forename: Annegret
authors.initials: A
authors.lastname: Boge
authors.forename: Dan
authors.initials: D
authors.lastname: Hallén
authors.forename: Kim Y C
authors.initials: KY
authors.lastname: Fung
authors.forename: Mark W
authors.initials: MW
authors.lastname: Duncan
authors.forename: Niels
authors.initials: N
authors.lastname: Andersen
authors.forename: Avram
authors.initials: A
authors.lastname: Goldstein
authors.forename: Lennart
authors.initials: L
authors.lastname: Olsson
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003124:Colorimetry; D003488:Cyanogen Bromide; D004921:Erythropoietin / Q000378:metabolism; D005110:Extracellular Space / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D008970:Molecular Weight; D017467:Receptors, Erythropoietin / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D007202:Indicators and Reagents; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D003488:Cyanogen Bromide