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: 8.46). 06/2007; 26(22):3122-42. DOI: 10.1038/sj.onc.1210407
Source: PubMed


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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    • "Specifically, it was reported that GPRs were regulated in response to TBI in rat brain [52]. One example of GPR-mediated signal transduction is MAPK pathway [53], which was also enriched by GO term analysis. MAPK signaling cascades consist of three main kinase pathways: extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK, which are sensitive to various environmental change and stress conditions [54]. "
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    • "T, Supporting information). These genes are involved in signalling cascades initiating cell proliferation and differentiation (Ip & Davis 1998; Goldsmith & Dhanasekaran 2007 "
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    • "Both G-protein and β-arrestin mediated signaling pathways can lead to ERK activation [30, 32]. The activation of ERK cascades through G-protein α subunits including Gs, Gi, and Gq and G-protein βγ subunit signaling to Ras has been described [33-39]. "
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