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PMID:1331173

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Citation

Gorn, AH, Lin, HY, Yamin, M, Auron, PE, Flannery, MR, Tapp, DR, Manning, CA, Lodish, HF, Krane, SM and Goldring, SR (1992) Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line. J. Clin. Invest. 90:1726-35

Abstract

A human ovarian small cell carcinoma line (BIN-67) expresses abundant calcitonin (CT) receptors (CTR) (143,000 per cell) that are coupled, to adenylate cyclase. The dissociation constants (Kd) for the CTRs on these BIN-67 cells is approximately 0.42 nM for salmon CT and approximately 4.6 nM for human CT. To clone a human CTR (hCTR), a BIN-67 cDNA library was screened using a cDNA probe from a porcine renal CTR (pCTR) that we recently cloned. One positive clone of 3,588 bp was identified. Transfection of this cDNA into COS cells resulted in expression of receptors with high affinity for salmon CT (Kd = approximately 0.44 nM) and for human CT (Kd = approximately 5.4 nM). The expressed hCTR was coupled to adenylate cyclase. Northern analysis with the hCTR cDNA probe indicated a single transcript of approximately 4.2 kb. The cloned cDNA encodes a putative peptide of 490 amino acids with seven potential transmembrane domains. The amino acid sequence of the hCTR is 73% identical to the pCTR, although the hCTR contains an insert of 16 amino acids between transmembrane domain I and II. The structural differences may account for observed differences in binding affinity between the porcine renal and human ovarian CTRs. The CTRs are closely related to the receptors for parathyroid hormone-parathyroid hormone-related peptide and secretin; these receptors comprise a distinct family of G protein-coupled seven transmembrane domain receptors. Interestingly, the hCTR sequence is remotely related to the cAMP receptor of Dictyostelium discoideum (21% identical), but is not significantly related to other G protein-coupled receptor sequences now in the data bases.

Links

PubMed PMC443230 Online version:10.1172/JCI116046

Keywords

Amino Acid Sequence; Base Sequence; Cloning, Molecular; Cyclic AMP/biosynthesis; Female; Humans; Molecular Sequence Data; Ovarian Neoplasms/chemistry; Ovarian Neoplasms/pathology; RNA, Messenger/analysis; Receptors, Calcitonin; Receptors, Cell Surface/analysis; Receptors, Cell Surface/chemistry; Receptors, Cell Surface/genetics; Receptors, Cyclic AMP/analysis; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CALCR

involved_in

GO:0007189: adenylate cyclase-activating G protein-coupled receptor signaling pathway

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete


See also

References

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