title: Cloning and characterization of human urocortin.
abstract: Urocortin, a new member of the CRF peptide family which also includes urotensin I and sauvagine, was recently cloned from the rat midbrain. The synthetic replicate of urocortin was found to bind with high affinity to type 1 and type 2 CRF receptors and, based upon its anatomic localization within the brain, was proposed to be a natural ligand for the type 2 CRF receptors. Using a genomic library, we have cloned the human counterpart of rat urocortin and localized it to human chromosome 2. Human and rat urocortin share 95% identity within the mature peptide region. Synthetic human urocortin binds with high affinity to CRF receptor types 1, 2 alpha, and 2 beta, stimulates cAMP accumulation from cells stably transfected with these receptors, and acts in vitro to release ACTH from dispersed rat anterior pituitary cells. In addition, the CRF-binding protein binds human urocortin with high affinity and can prevent urocortin-stimulated ACTH secretion in vitro. The inhibitory effect of the CRF-binding protein on human urocortin can be blocked by biologically inactive CRF fragments, such as CRF(9-33).
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla 92037, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Donaldson
authors.forename: S W
authors.initials: SW
authors.lastname: Sutton
authors.forename: M H
authors.initials: MH
authors.lastname: Perrin
authors.forename: A Z
authors.initials: AZ
authors.lastname: Corrigan
authors.forename: K A
authors.initials: KA
authors.lastname: Lewis
authors.forename: J E
authors.initials: JE
authors.lastname: Rivier
authors.forename: J M
authors.initials: JM
authors.lastname: Vaughan
authors.forename: W W
authors.initials: WW
authors.lastname: Vale
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D017385:Sequence Homology; D014162:Transfection; D054832:Urocortins
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP