Article

G Protein regulation of MAPK networks

Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Oncogene (Impact Factor: 8.56). 06/2007; 26(22):3122-42. DOI: 10.1038/sj.onc.1210407
Source: PubMed

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 G(s), G(i), G(q) and G(12) families, regulate ERK1/2, JNK, p38MAPK, ERK5 and ERK6 modules by different mechanisms. The alpha- as well as betagamma-subunits are involved in the regulation of these MAPK modules in a context-specific manner. While the alpha- and betagamma-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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    • "activation of G-protein by hormones and neurotransmitters, the increased concentration of intracellular calcium, the combination of receptor tyrosine kinase (RTK) with growth factors and cytokines, and stimulation of extracellular matrix to integrin. It was reported that G-protein regulated MAPK by Ras-dependent and Rap1-dependent pathway (paths 1, 7–9 and 11) (Goldsmith and Dhanasekaran 2007; May and Hill 2008). Characteristic intracellular Ca 2+ oscillations also activated MAPK cascade in hepatocyte proliferation after rat 2/3 hepatectomy (path 2) (Kitamura et al. 1995). "
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    Journal of Genetics 12/2011; 90(3):435-42. DOI:10.1007/s12041-011-0107-5 · 1.01 Impact Factor
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