Human calcitonin receptors exhibit agonist-independent (constitutive) signaling activity

David P. Cohen, Colette N. Thaw, Anjali Varma, Marvin C. Gershengorn, Daniel R. Nussenzveig

Research output: Contribution to journalArticle

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Abstract

The human CT receptor (hCTR), which is found as three isoforms, belongs to a small, recently described subfamily of G protein-coupled receptors (GPCRs). Several mutant GPCRs have been shown to exhibit constitutive (or agonist-independent) signaling activity and cause disease in humans, but only a few GPCRs have been identified with agonist-independent activity in the wild-type (or native) form. In the hCTR subfamily, no wild-type receptor has been shown to exhibit constitutive activity and only one, a mutated receptor for PTH/PTH-related peptide, has been found with constitutive activity to cause disease in humans. We demonstrate that two wild-type isoforms of hCTR, hCTR-1 and hCTR-2, exhibit constitutive activity by showing that they cause elevation of cAMp and induction of a cAMP-responsive gene in two cell types in culture in the absence of agonist. The identical mutation that caused the PTH/PTH-related peptide receptor to be constitutively active was made in hCTR-2 and shown to have no effect on signaling. We suggest that constitutive activity of wild-type hCTR-1 and hCTR-2 may reflect an adaptation of their signaling properties to exert their regulatory function in the absence of agonist in some cell types.

Original languageEnglish (US)
Pages (from-to)1400-1405
Number of pages6
JournalEndocrinology
Volume138
Issue number4
DOIs
StatePublished - Jan 1 1997

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ASJC Scopus subject areas

  • Endocrinology

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