Cloning and characterization of human urocortin.
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).
Donaldson
C J
CJ
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla 92037, USA.
Sutton
S W
SW
Perrin
M H
MH
Corrigan
A Z
AZ
Lewis
K A
KA
Rivier
J E
JE
Vaughan
J M
JM
Vale
W W
WW
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
D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP