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

25 Citations (Scopus)

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 - 1997

Fingerprint

Calcitonin Receptors
G-Protein-Coupled Receptors
Protein Isoforms
Parathyroid Hormone Receptor Type 1
Parathyroid Hormone-Related Protein
Mutant Proteins
Human Activities
Cell Culture Techniques

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Human calcitonin receptors exhibit agonist-independent (constitutive) signaling activity. / Cohen, David P.; Thaw, Colette N.; Varma, Anjali; Gershengorn, Marvin C.; Nussenzveig, Daniel R.

In: Endocrinology, Vol. 138, No. 4, 1997, p. 1400-1405.

Research output: Contribution to journalArticle

Cohen, David P. ; Thaw, Colette N. ; Varma, Anjali ; Gershengorn, Marvin C. ; Nussenzveig, Daniel R. / Human calcitonin receptors exhibit agonist-independent (constitutive) signaling activity. In: Endocrinology. 1997 ; Vol. 138, No. 4. pp. 1400-1405.
@article{99bc5ea607a34e3c87a3b7da1a73af5b,
title = "Human calcitonin receptors exhibit agonist-independent (constitutive) signaling activity",
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.",
author = "Cohen, {David P.} and Thaw, {Colette N.} and Anjali Varma and Gershengorn, {Marvin C.} and Nussenzveig, {Daniel R.}",
year = "1997",
doi = "10.1210/en.138.4.1400",
language = "English (US)",
volume = "138",
pages = "1400--1405",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Human calcitonin receptors exhibit agonist-independent (constitutive) signaling activity

AU - Cohen, David P.

AU - Thaw, Colette N.

AU - Varma, Anjali

AU - Gershengorn, Marvin C.

AU - Nussenzveig, Daniel R.

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0030960824&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030960824&partnerID=8YFLogxK

U2 - 10.1210/en.138.4.1400

DO - 10.1210/en.138.4.1400

M3 - Article

C2 - 9075694

AN - SCOPUS:0030960824

VL - 138

SP - 1400

EP - 1405

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -