ERK1/2 activation

KohoutTA, Nicholas SL, Perry SJ, Reinhart G, Junger S, Struthers RS. Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. J Biol Chem 2004 279(22) 23214-23222. 

Inhibitors of Tpl-2 (MKKK), MEK1/2 (MKK1/2) and ERK1/2 have been reported. Macrophages from Tpl-2 knockout mice lack ERK1/2 activation leading to loss of TNFa expression and are insensitive to LPS-induced endotoxin shock [9]. Inhibition of Tpl-2 and MEK1/2 produces potent anti-inflammatory effects in cellular and animal models. 

ERK1/2 activation by Ang II, which can be blocked by PLC inhibition, intracellular Ca2+ chelation, and tyrosine kinase inhibition, eventually proceeds through a Ras-dependent pathway (Eguchi et al. 1996). One intermediate tyrosine kinase... 

Fig. 6.3 Proposed model for the Gq-dependent and 3-arrestin2-dependent pathways of ERK1/2 activation. In the Gq-dependent pathway, ERK1/2 translocates to the nucleus while activation of ERK1/2 by the 3-arrestin2 scaffold leads to the sequestration of active ERK1/2 in the cytoplasm, where it activates RSK (see Figure 6.2). The proposed scheme maintains that the Gq-dependent pathway leads to cellular hypertrophy while cytosolic ERK1/2 promotes cell proliferation.

Godeny, M.D., and Sayeski, P.P. 2006a. ANG Il-induced cell proliferation is dually mediated by c-Src/Yes/Fyn-regulated ERK1/2 activation in the cytoplasm and PKCC-controlled ERK1/2 activity within the nucleus. Am. J. Physiol. 291 C1297-1307. 

Takahashi M, Berk BC. Mitogen activated protein kinase (ERK1/2) activation by shear stress and adhesion in endothelial cells. Essential role for a herbimycin-sensitive kinase. J Clin Invest. 1996 98 2623-2631. 

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