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 th...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 1996-05, Vol.137 (5), p.2167-2170
Main Authors: Donaldson, C J, Sutton, S W, Perrin, M H, Corrigan, A Z, Lewis, K A, Rivier, J E, Vaughan, J M, Vale, W W
Format: Article
Language:English
Subjects:
Adrenocorticotropic hormone
Affinity
Biological effects
Chromosome 2
Cloning
Localization
Mesencephalon
Peptides
Pituitary (anterior)
Proteins
Receptors
Urocortin
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Summary: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).
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.137.5.8612563