Participation of transmembrane proline 82 in angiotensin II AT(1) receptor signal transduction

Participation of transmembrane proline 82 in angiotensin II AT(1) receptor signal transduction

Author Reis, Rosana I. Google Scholar
Santos, Edson L. Google Scholar
Pesquero, Joao B. Google Scholar
Oliveira, Laerte Google Scholar
Schanstra, Joost P. Google Scholar
Bascands, Jean-Loup Google Scholar
Pecher, Christiane Google Scholar
Paiva, Antonio C. M. Google Scholar
Costa-Neto, Claudio M. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
INSERM
Univ Toulouse 3
Abstract Most of the classical physiological effects of the octapeptide angiotensin II (AngII) are produced by activating the AT, receptor which belongs to the G-protein coupled receptor family (GPCR). Peptidic GPCRs may be functionally divided in three regions: (i) extracellular domains involved in ligand binding; (ii) intracellular domains implicated in agonist-induced coupling to G protein and (iii) seven transmembrane domains (TM) involved in signal transduction. the TM regions of such receptors have peculiar characteristics such as the presence of proline residues. in this project we aimed to investigate the participation of two highly conserved proline residues (Pro82 and Pro162), located in TM II and TM IV, respectively, in AT1 receptor signal transduction. Both mutations did not cause major alterations in AngII affinity. Functional assays indicated that the P162A mutant did not influence the signal transduction. On the other hand, a potent deleterious effect of P82A mutation on signal transduction was observed. We believe that the Pro82 residue is crucial to signal transduction, although it is not possible to say yet if this is due to a direct participation or if due to a structural rearrangement of TM II. in this last hypothesis, the removal of proline residue might be correlated to a removal of a kink, which in turn can be involved in the correct positioning of residues involved in signal transduction. (c) 2006 Elsevier B.V. All rights reserved.
Keywords site-directed mutagenesis
signal transduction
G-protein coupled receptors
agonist
Language English
Date 2007-04-05
Published in Regulatory Peptides. Amsterdam: Elsevier B.V., v. 140, n. 1-2, p. 32-36, 2007.
ISSN 0167-0115 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 32-36
Origin http://dx.doi.org/10.1016/j.regpep.2006.11.028
Access rights Closed access
Type Article
Web of Science ID WOS:000245151700006
URI http://repositorio.unifesp.br/handle/11600/29660

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