Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart.
Corticotropin-releasing factor (CRF; corticoliberin) regulates the secretion of corticotropin (ACTH) and beta-endorphin and has a broad range of effects on the nervous, endocrine, reproductive, cardiovascular, gastrointestinal, and immune systems. Recently, human, rat, and mouse CRF receptors (CRF-R) have been cloned and functionally and anatomically characterized. We report here the cloning of a second CRF-R cDNA (CRF-RB), which encodes a protein of 431 amino acids, which is 16 amino acids longer and 68% similar to the previously cloned CRF-R, CRF-RA. When transiently expressed in COS-M6 cells, CRF-RB binds CRF with high affinity [Kd = 1.2 (0.57-2.5)nM] and transduces the CRF-stimulated signal of the accumulation of intracellular cAMP, which is inhibited by a CRF antagonist. Comparison of the amino acid sequences of CRF-RB and the previously cloned receptor reveals major differences in the N-terminal domain and in the extracellular loops, whereas the sequences of the intracellular loops are nearly identical. CRF-RB and related transcripts are expressed in the heart, as well as in other tissues, including the gastrointestinal tract, epididymis, and brain.
Perrin
M
M
Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA, USA.
Donaldson
C
C
Chen
R
R
Blount
A
A
Berggren
T
T
Bilezikjian
L
L
Sawchenko
P
P
Vale
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D015870:Gene Expression; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney; D007700:Kinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D000242:Cyclic AMP