Roles of intraloops-2 and -3 and the proximal C-terminus in signalling pathway selection from the human calcium-sensing receptor.

Autor: Goolam MA; School of Molecular Bioscience, University of Sydney, NSW 2006, Australia., Ward JH; School of Molecular Bioscience, University of Sydney, NSW 2006, Australia., Avlani VA; School of Molecular Bioscience, University of Sydney, NSW 2006, Australia., Leach K; Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia., Christopoulos A; Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia., Conigrave AD; School of Molecular Bioscience, University of Sydney, NSW 2006, Australia. Electronic address: arthur.conigrave@sydney.edu.au.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2014 Sep 17; Vol. 588 (18), pp. 3340-6. Date of Electronic Publication: 2014 Jul 28.
DOI: 10.1016/j.febslet.2014.07.022
Abstrakt: The calcium-sensing receptor (CaSR) couples to signalling pathways via intracellular loops 2 and 3, and the C-terminus. However, the requirements for signalling are largely undefined. We investigated the impacts of selected point mutations in iL-2 (F706A) and iL-3 (L797A and E803A), and a truncation of the C-terminus (R866X) on extracellular Ca(2+) (Ca(2+)o)-stimulated phosphatidylinositol-specific phospholipase-C (PI-PLC) and various other signalling responses. CaSR-mediated activation of PI-PLC was markedly attenuated in all four mutants and similar suppressions were observed for Ca(2+)o-stimulated ERK1/2 phosphorylation. Ca(2+)o-stimulated intracellular Ca(2+) (Ca(2+)i) mobilization, however, was relatively preserved for the iL-2 and iL-3 mutants and suppression of adenylyl cyclase was unaffected by either E803A or R866X. The CaSR selects for specific signalling pathways via the proximal C-terminus and key residues in iL-2, iL-3.
(Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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