Betagamma subunits of G(i/o) suppress EGF-induced ERK5 phosphorylation, whereas ERK1/2 phosphorylation is enhanced

Cellular Signalling
Yutaro ObaraNorimichi Nakahata

Abstract

Extracellular signal-regulated kinases (ERKs) play important physiological roles in proliferation, differentiation and gene expression. ERK5 is twice the size of ERK1/2, the amino-terminal half contains the kinase domain that shares the homology with ERK1/2 and TEY activation motif, whereas the carboxy-terminal half is unique. In this study, we examined the cross-talk mechanism between G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases, focusing on ERK1/2 and 5. The pretreatment of rat pheochromocytoma cells (PC12) with pertussis toxin (PTX) specifically enhanced epidermal growth factor (EGF)-induced ERK5 phosphorylation. In addition, lysophosphatidic acid (LPA) attenuated the EGF-induced ERK5 phosphorylation in LPA(1) receptor- and G(i/o)-dependent manners. On the other hand, LPA alone activated ERK1/2 via Gbetagamma subunits and Ras and potentiated EGF-induced ERK1/2 phosphorylation at late time points. These results suggest G(i/o) negatively regulates ERK5, while it positively regulates ERK1/2. LPA did not affect cAMP levels after EGF treatment, and the reagents promoting cAMP production such as forskolin and cholera toxin also attenuated the EGF-induced ERK5 phosphorylation, indicating that the inhibitory eff...Continue Reading

References

Apr 1, 1993·Trends in Biochemical Sciences·E Nishida, Y Gotoh
Nov 1, 2000·Cell·J Schlessinger
Jul 24, 2004·Seminars in Cell & Developmental Biology·Brigitte Anliker, Jerold Chun
Nov 18, 2004·Journal of Cell Science·Yutaro ObaraPhilip J S Stork
May 15, 2007·Oncogene·Z G Goldsmith, D N Dhanasekaran

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Citations

May 15, 2013·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Yutaro Obara
Jul 20, 2014·The Journal of Biological Chemistry·Robert B LaprairieEileen M Denovan-Wright
Oct 17, 2015·Molecular and Cellular Biochemistry·Francisco J Rodríguez-ÁlvarezMa José Toro
Jun 8, 2011·Journal of Neuroscience Research·Chang SuMeharvan Singh

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