Mitogen-activated protein kinases translocation

The catalytic activity of cPLA2 is stimulated by phosphorylation catalyzed by the mitogen-activated protein kinase (MAPK) at Ser505. This modification stimulates enzyme activity only, indicating that translocation and phosphorylation are independent mechanisms of cPLA2 regulation [21]. 

Capano, M., and Crompton, M. 2006. Bax translocates to mitochondria of heart cells during simulated ischaemia involvement of AMP-activated and p38 mitogen-activated protein kinases. Biochem J 39 57-64. 

Trask, O.J., Jr. et al. 2006. Assay development and case history of a 32K-biased library high-content MK2-EGFP translocation screen to identify p38 mitogen-activated protein kinase inhibitors on the Array Scan 3.1 imaging platform. Meth. Enzymol. 414, 419-439. 

After receptor interaction, AMPs may activate mediators of the mitogen-activated protein-kinase signal transduction pathways [189,202,203,205], induce calcium (Ca ) mobilization [183,189], bind to SH3-domain-containing proteins [206,207], or inhibit LPS-induced NF-kB nuclear translocation [196,208]. 

Fig. 5.n Activation of the MAPK cascade via/ -arrestin and C protein-coupled receptors. A complex is formed between / -arrestin and the various components of a MAPK module (see Chapter 10) in the cytosol. This multiprotein complex translocates to the plasma membrane bound receptor following ligand binding. / -arrestin functions as a scaffold for the MAPK module and promotes internalization of the whole complex. This leads to generation of active MAPK and stimulation of transcription. MAPK mitogen activated protein kinase, MEK MAPK/ERK kinase, MEKK MEK kinase. 

Shou Y, Li L, Prabhakaran K et al. (2003). p45 Mitogen-activated protein kinase contributes to Bax translocation and cytochrome c release in cyanide-induced apoptosis. Toxicol Sci, 75, 99-107. 

A critical site is Ser-505, the site phosphorylated by mitogen-activated protein kinase. Phosphorylation at this site increases the activity of the enzyme both in vitro and in vivo. However, other phosphorylation sites may also be involved in particular, Ser-727 may also have an important role in some cell systems [23]. The Ser-505 is located in a flexible loop that connects the C2 and catalytic domains (Fig. 9). It is possible that phosphorylation of this residue produces the optimum orientation of the two domains with respect to the membrane interface (S. Das, 2003). Overall, it is probable that the role of phosphorylation in translocation, membrane binding, and enzyme activation depends on the cell type and the nature of the stimulus [23]. 

Some cytokines. The IL-6 class cytokine oncostatin M (OSM), IL-1 and TNFa of monocyte-macrophage derivation are activators of the jak gene and thus the JAK/STAT and/or JAK/MAPK pathways in fibroblast-like synoviocytes of RA. These cells overproduce BL-6 and MMPs, harbor an activated JAK gene, and allow intranuclear translocation of the phosphoiylated STAT protein dimers. The specific inhibitor of OSM, CP690,550 may reverse the entire process. The p38 mitogen-activated protein kinase (MAPK) with the member of its group, the c-Jun... 

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