May 2010

[JBC] A New Trick for G-alpha-q

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A model for the structural relationship of the G-alpha-q-PKC-zeta-MEK5 complex in controlling ERK5 activation.

Signal transduction cascades allow cells to regulate coordinated responses to extracellular stimuli such as heat, hormones and mitogens. Surface-associated G protein-coupled receptors (GPCR) respond to extracellular molecules, activating signal transduction pathways that direct changes in cellular responses, such as gene expression. Stimulation of the Gq-coupled GPCR leads to the activation of extracellular signal regulated kinase-5 (ERK5) through a previously unknown mechanism. In this study, the researchers elucidate the signal transduction network between a Gq-coupled GPCR and ERK5.Their research shows that an atypical protein kinase C, PKC zeta, is required for GPCR-mediated ERK5 activation. Most interesting, perhaps, is that PKC zeta and MEK5, which is an activator of ERK5, are shown to physically interact via the G protein subunit, G-alpha-q. Upon GPCR activation, the trimeric MEK5-G-alpha-q-PKC zeta complex appears to be required for ERK5. Together, this work demonstrates a novel function for G-alpha-q as an adaptor protein that facilitates GPCR signaling by mediating MEK5-PKC zeta protein-protein interactions. Furthermore, G-alpha-q may serve as an adaptor protein in other PKC zeta-mediated signaling cascades, a possibility that enhances the current view of cellular signal transduction. 

G-alpha-q Acts as an Adaptor Protein in Pkc-zeta-mediated ERK5 Activation by GPCR

Garlota Garcia-Hoz, Guzmán Sánchez-Fernández, Maria Teresa Díaz-Meco, Jorge Moscat, Federico Mayor and Catalina Ribas

J. Biol. Chem., published online March 3, 2010 

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