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J. Biol. Chem. 285 (18): 13480-13489

© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

G{alpha}q Acts as an Adaptor Protein in Protein Kinase C{zeta} (PKC{zeta})-mediated ERK5 Activation by G Protein-coupled Receptors (GPCR)*Formula {diamondsuit}

Carlota García-Hoz{ddagger}§, Guzmán Sánchez-Fernández{ddagger}§, Maria Teresa Díaz-Meco, Jorge Moscat, Federico Mayor{ddagger}§1, , and Catalina Ribas{ddagger}§2

From the {ddagger}Departamento de Biología Molecular and
the §Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain and
the Department of Genome Science, Genome Research Institute, University of Cincinnati, Cincinnati, Ohio 45221

ABSTRACT Back to Top

Abstract: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of different cellular functions. These receptors can regulate a highly interconnected network of biochemical routes that control the activity of several members of the mitogen-activated protein kinase (MAPK) family. The ERK5 MAPK has been shown to be activated by Gq-coupled GPCR via unknown mechanisms. We find that the atypical protein kinase C (PKC{zeta}), previously reported to interact with the ERK5 activator MEK5 and to be involved in epidermal growth factor-mediated ERK5 stimulation, plays a crucial role in the activation of the ERK5 pathway by Gq-coupled GPCR. Stimulation of ERK5 by Gq-coupled GPCR is abolished upon pharmacological inhibition of PKC{zeta} as well as in embryonic fibroblasts obtained from PKC{zeta}-deficient mice. Both PKC{zeta} and MEK5 associate to G{alpha}q upon activation of GPCR, thus forming a ternary complex that seems essential for the activation of ERK5. These data put forward a novel function of G{alpha}q as a scaffold protein involved in the modulation of the ERK5 cascade by GPCR that could be relevant in Gq-mediated physiological functions.

Key Words: Adaptor Proteins • G Protein-coupled Receptors (GPCR) • G Proteins • MAP Kinases (MAPKs) • Signal Transduction • ERK5 • G&{alpha}q • MEK5 • PKC&{zeta}

Received for publication January 2, 2010. Revision received March 2, 2010.

1 To whom correspondence may be addressed. Tel.: 34-91-1964640; Fax: 34-91-1964420; E-mail: fmayor{at}cbm.uam.es.

2 To whom correspondence may be addressed. Tel.: 34-91-1964640; Fax: 34-91-1964420; E-mail: cribas{at}cbm.uam.es.

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