Title | G alpha(q) acts as an adaptor protein in protein kinase C zeta (PKCzeta)-mediated ERK5 activation by G protein-coupled receptors (GPCR). |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | García-Hoz C, Sánchez-Fernández G, Diaz-Meco MTeresa, Moscat J, Mayor F, Ribas C |
Journal | J Biol Chem |
Volume | 285 |
Issue | 18 |
Pagination | 13480-9 |
Date Published | 2010 Apr 30 |
ISSN | 1083-351X |
Keywords | Animals, Chlorocebus aethiops, COS Cells, Embryo, Mammalian, Enzyme Activation, GTP-Binding Protein alpha Subunits, Gq-G11, Humans, MAP Kinase Kinase 5, MAP Kinase Signaling System, Mice, Mice, Mutant Strains, Mitogen-Activated Protein Kinase 7, Multiprotein Complexes, NIH 3T3 Cells, Protein Kinase C, Protein Structure, Quaternary, Receptors, G-Protein-Coupled |
Abstract | G(q)-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 G(q)-coupled GPCR via unknown mechanisms. We find that the atypical protein kinase C (PKCzeta), 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 G(q)-coupled GPCR. Stimulation of ERK5 by G(q)-coupled GPCR is abolished upon pharmacological inhibition of PKCzeta as well as in embryonic fibroblasts obtained from PKCzeta-deficient mice. Both PKCzeta 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 G(q)-mediated physiological functions. |
DOI | 10.1074/jbc.M109.098699 |
Alternate Journal | J Biol Chem |
PubMed ID | 20200162 |
PubMed Central ID | PMC2859508 |
Related Faculty:
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.