A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor
Open Access
- 1 April 1999
- journal article
- Published by Wiley in FEBS Letters
- Vol. 448 (1) , 180-184
- https://doi.org/10.1016/s0014-5793(99)00368-3
Abstract
A missense mutation, A843E, in the seventh transmembrane domain of the human Ca2+ receptor, identified in a subject with autosomal dominant hypocalcemia, was found to cause a constitutive activation while at the same time lowering the maximal response of the receptor to Ca2+. A truncated human Ca2+ receptor lacking the majority of the N‐terminal extracellular domain failed to respond to Ca2+ despite an excellent cell surface expression. The A843E mutant version of this truncated receptor showed constitutive activation. These results identify A843 as a critical residue for maintaining the inactive conformation of the human Ca2+ receptor. Substitution of glutamate, but not lysine or valine, for alanine 843 leads to activation of the human Ca2+ receptor in a manner that no longer depends upon Ca2+ binding to the extracellular domain.Keywords
This publication has 26 references indexed in Scilit:
- Constitutive activity of receptors coupled to guanine nucleotide regulatory proteinsPublished by Elsevier ,2002
- A Unique Constitutively Activating Mutation in Third Transmembrane Helix of Luteinizing Hormone Receptor Causes Sporadic Male Gonadotropin-Independent Precocious PubertyJournal of Clinical Endocrinology & Metabolism, 1998
- The Extracellular Calcium-Sensing Receptor: Its Role in Health and DiseaseAnnual Review of Medicine, 1998
- Monoclonal Antibodies Against Synthetic Peptides Corresponding to the Extracellular Domain of the Human Ca2+ Receptor: Characterization and Use in Studying Concanavalin A InhibitionJournal of Bone and Mineral Research, 1997
- Sporadic Hypoparathyroidism Caused by de Novo Gain- of-Function Mutations of the Ca2+-Sensing ReceptorJournal of Clinical Endocrinology & Metabolism, 1997
- Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidismHuman Molecular Genetics, 1996
- Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroidNature, 1993
- A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious pubertyNature, 1993
- The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteinsNeuron, 1993
- Phorbol esters modulate the high Ca2+-stimulated accumulation of inositol phosphates in bovine parathyroid cellsJournal of Bone and Mineral Research, 1990