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Sci. Signal., 4 May 2010
Vol. 3, Issue 120, p. ec131
[DOI: 10.1126/scisignal.3120ec131]

EDITORS' CHOICE

G Protein Signaling Adaptable G Protein

John F. Foley

Science Signaling, AAAS, Washington, DC 20005, USA

The main members of the mitogen-activated protein kinase (MAPK) family, extracellular signal–regulated kinases (ERKs) 1 and 2, c-Jun N-terminal kinase, and p38, are well characterized and regulate such cellular responses as proliferation and differentiation. In contrast, less is known about the regulation of the more recent additions to the MAPK family, such as ERK5, which is activated by various growth factor receptors, cytokine receptors, and Gq-coupled G protein–coupled receptors (GPCRs). In response to epidermal growth factor, activation of ERK5 requires the MAPK kinase MEK5 and the atypical protein kinase C isoform PKC{zeta}; however, how ERK5 is activated by GPCRs is unclear. García-Hoz et al. found that stimulation of m1 muscarinic acetylcholine receptors led to the phosphorylation and activation of ERK5 in NIH 3T3 cells, which was independent of Src family kinases, EGF receptors, and phospholipase C–β (PLC-β), an effector of G{alpha}q that leads to the activation of ERK1/2. Stimulation of another Gq-coupled GPCR led to the activation of ERK5 in wild-type, but not in PKC{zeta}-deficient, mouse embryonic fibroblasts, and coimmunoprecipitation studies showed that G{alpha}q physically associated with PKC{zeta}. Immunoprecipitated complexes of tagged G{alpha}q and PKC{zeta} proteins contained MEK5. MEK5 and PKC{zeta} contain PB1 domains through which they can interact; however, a PB1 domain–deficient mutant of MEK5 was found in immunoprecipitated complexes of G{alpha}q and PKC{zeta}. In addition to suggesting roles for MEK5 and PKC{zeta} as effectors of G{alpha}q, this study also suggests that G{alpha}q acts as a scaffold protein that independently binds to MEK5 and PKC{zeta} to mediate the activation of ERK5.

C. García-Hoz, G. Sánchez-Fernández, M. T. Díaz-Meco, J. Moscat, F. Mayor, C. Ribas, G{alpha}q acts as an adaptor protein in protein kinase C{zeta} (PKC{zeta})-mediated ERK5 activation by G protein-coupled receptors (GPCR). J. Biol. Chem. 285, 13480–13489 (2010). [Abstract] [Full Text]

Citation: J. F. Foley, Adaptable G Protein. Sci. Signal. 3, ec131 (2010).


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