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Title

Gαq signalling: The new and the old

AuthorsSánchez-Fernández, Guzmán ; Cabezudo, Sofía ; García-Hoz, Carlota; Benincá, Cristiane ; Aragay, Anna M. ; Mayor Menéndez, Federico ; Ribas, Catalina
KeywordsG protein
G-protein coupled receptors
Gq
Interactome
Signalling pathways
Issue DateMay-2014
PublisherElsevier
CitationCellular Signalling 26(5): 833-848 (2014)
AbstractIn the last few years the interactome of Gαq has expanded considerably, contributing to improve our understanding of the cellular and physiological events controlled by this G alpha subunit. The availability of high-resolution crystal structures has led the identification of an effector-binding region within the surface of Gαq that is able to recognise a variety of effector proteins. Consequently, it has been possible to ascribe different Gαq functions to specific cellular players and to identify important processes that are triggered independently of the canonical activation of phospholipase Cβ (PLCβ), the first identified Gαq effector. Novel effectors include p63RhoGEF, that provides a link between G protein-coupled receptors and RhoA activation, phosphatidylinositol 3-kinase (PI3K), implicated in the regulation of the Akt pathway, or the cold-activated TRPM8 channel, which is directly inhibited upon Gαq binding. Recently, the activation of ERK5 MAPK by Gq-coupled receptors has also been described as a novel PLCβ-independent signalling axis that relies upon the interaction between this G protein and two novel effectors (PKCφ and MEK5). Additionally, the association of Gαq with different regulatory proteins can modulate its effector coupling ability and, therefore, its signalling potential. Regulators include accessory proteins that facilitate effector activation or, alternatively, inhibitory proteins that downregulate effector binding or promote signal termination. Moreover, Gαq is known to interact with several components of the cytoskeleton as well as with important organisers of membrane microdomains, which suggests that efficient signalling complexes might be confined to specific subcellular environments. Overall, the complex interaction network of Gαq underlies an ever-expanding functional diversity that puts forward this G alpha subunit as a major player in the control of physiological functions and in the development of different pathological situations. © 2014 Elsevier Inc.
Publisher version (URL)http://dx.doi.org/10.1016/j.cellsig.2014.01.010
URIhttp://hdl.handle.net/10261/124276
DOI10.1016/j.cellsig.2014.01.010
Identifiersdoi: 10.1016/j.cellsig.2014.01.010
issn: 0898-6568
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