Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor.
The corticotropin-releasing factor (CRF) family of neuropeptides includes the mammalian peptides CRF, urocortin, and urocortin II, as well as piscine urotensin I and frog sauvagine. The mammalian peptides signal through two G protein-coupled receptor types to modulate endocrine, autonomic, and behavioral responses to stress, as well as a range of peripheral (cardiovascular, gastrointestinal, and immune) activities. The three previously known ligands are differentially distributed anatomically and have distinct specificities for the two major receptor types. Here we describe the characterization of an additional CRF-related peptide, urocortin III, in the human and mouse. In searching the public human genome databases we found a partial expressed sequence tagged (EST) clone with significant sequence identity to mammalian and fish urocortin-related peptides. By using primers based on the human EST sequence, a full-length human clone was isolated from genomic DNA that encodes a protein that includes a predicted putative 38-aa peptide structurally related to other known family members. With a human probe, we then cloned the mouse ortholog from a genomic library. Human and mouse urocortin III share 90% identity in the 38-aa putative mature peptide. In the peptide coding region, both human and mouse urocortin III are 76% identical to pufferfish urocortin-related peptide and more distantly related to urocortin II, CRF, and urocortin from other mammalian species. Mouse urocortin III mRNA expression is found in areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex; it is also expressed peripherally in small intestine and skin. Urocortin III is selective for type 2 CRF receptors and thus represents another potential endogenous ligand for these receptors.
Lewis
K
K
Clayton Foundation Laboratories for Peptide Biology and Laboratory of Neuronal Structure and Function, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Li
C
C
Perrin
M H
MH
Blount
A
A
Kunitake
K
K
Donaldson
C
C
Vaughan
J
J
Reyes
T M
TM
Gulyas
J
J
Fischer
W
W
Bilezikjian
L
L
Rivier
J
J
Sawchenko
P E
PE
Vale
W W
WW
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D003346:Corticotropin-Releasing Hormone / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection; D054832:Urocortins
C101531:CRF receptor type 2; D010446:Peptide Fragments; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D054832:Urocortins; C518358:urocortin 2, mouse; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP