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G Protein regulation of MAPK networks

Abstract

G proteins provide signal-coupling mechanisms to heptahelical cell surface receptors and are critically involved in the regulation of different mitogen-activated protein kinase (MAPK) networks. The four classes of G proteins, defined by the Gs, Gi, Gq and G12 families, regulate ERK1/2, JNK, p38MAPK, ERK5 and ERK6 modules by different mechanisms. The α- as well as βγ-subunits are involved in the regulation of these MAPK modules in a context-specific manner. While the α- and βγ-subunits primarily regulate the MAPK pathways via their respective effector-mediated signaling pathways, recent studies have unraveled several novel signaling intermediates including receptor tyrosine kinases and small GTPases through which these G-protein subunits positively as well as negatively regulate specific MAPK modules. Multiple mechanisms together with specific scaffold proteins that can link G-protein-coupled receptors or G proteins to distinct MAPK modules contribute to the context-specific and spatio-temporal regulation of mitogen-activated protein signaling networks by G proteins.

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Acknowledgements

The study was supported by a grant from NIH (GM 49897). Critical reading of the paper by Dr Rashmi Kumar and Mr Jake Gardner are gratefully acknowledged.

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Correspondence to D N Dhanasekaran.

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Goldsmith, Z., Dhanasekaran, D. G Protein regulation of MAPK networks. Oncogene 26, 3122–3142 (2007). https://doi.org/10.1038/sj.onc.1210407

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