MAPK, activation

Guyton, K. Z. Gorospe, M. Kensler, T. W. Holbrook, N. J. Mitogen-activated protein kinase (MAPK) activation by butylated hydroxytoluene hydroperoxide implications for cellular survival and tumor promotion. Cancer Res. 1996, 56, 3480-3485. 

Sun Y, Cheng Z, Ma L, Pei G. Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J Biol Chem 2002 277(51) 49212 19219. 

The levels of MAPK mRNA do not appear to change during the cell cycle instead, regulation of MAPK activity occurs post-translationally,... 

This intermediate MAPK activator (MAPK kinase, MAPKK) is a 45 kDa phosphoprotein capable of phosphorylating MAPK on serine/threonine and tyrosine residues (Matsuda et al., 1992 Nakielny et al., 1992a Kosako et al., 1993). Like MAPK, the activity of MAPKK is regulated by phosphorylation. During oocyte maturation MAPKK is phosphorylated on threonine residues (Kosako et al., 1992), and this phosphorylation is required for its activity (Ahn et al., 1991 Gomez and Cohen, 1991 Kosako et al., 1992 Matsuda et al., 1992). MPF can activate both MAPKK and MAPK in vitro, with the activation of MAPK lagging behind that of MAPKK however, MPF cannot activate either purified MAPKK or MAPK that has been dephosphorylated by phosphatases (Matsuda et al., 1992). MAPKK and MAPK are therefore believed to function downstream of MPF (Fig. 3). 

Kubiak We didn t see any change in the MAPK activity at that moment. Marcel Doree has looked carefully in Xenopus and concluded that MAPK was still active at the moment of inactivation of MPF. 

Vande Woude Certainly it is that way in Nenopus. Monica Murakami has published two couple of papers showing that the MAPK activity, prolonged after the p34 kinase destruction, is key to lengthening the first cycle to 60 min instead of 30 min. 

Roux, P. P., and Blenis, J. (2004). ERK and p38 MAPK-activated protein kinases A family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68, 320-344. 

Using chemical inhibitors of upstream kinases that potentially drive trichothecene-induced MAPK activation, two putative kinases have been identified double-stranded RNA- (dsRNA)-activated protein kinase (PKR)46 and hematopoietic cell kinase (Hck).47... 

The effect of MAPK activation on cellular processes that affect cell function and the resulting pharmacology has been delineated using modem techniques such as knock-out cells and animals [1,3,6]. Activation of MAPK in inflammatory cells such as T-cells, B-cells, macrophages and eosinophils leads to expression and/or activation of pro-inflammatory genes and mediators such as interleukin-1(3 (IL-1(3), TNFa, IL-6, chemokines [e.g., IL-8, macrophage inflammatory factor-1 a, (3 (MIP-la,[3)J, MMPs and toxic molecules such as free radicals and nitric oxide [1,3]. These pro-inflammatory mediators induce cellular proliferation, differentiation, survival, apoptosis and tissue degradation/destruction and help induce chronic inflammation. Inhibition of any one or more of the MAPK family... 

Ares, M.P., Pom-Ares, MI, Moses, S, Thyberg, J, Jrmtti-Berggren, L, Beiggien, P, Hultgardh-Nilsson, A, Kallin, B, Nilsson, J., 2000, Tbeta-hydroxycholesterol induces Ca(2-l-) oscillations, MAPK activation and apoptosis in human aortic smooth muscle cells, Atherosclerosis 153 2 3-35. 

Previous studies have reported that ERKs are characteristically associated with cell proliferation and protection from apoptosis (Bl, XI), while activation of JNK and p38 MAPK can promote apoptosis in many systems, including B lymphocytes (G5), cerebellar granule cells (K3), hematopoietic cells (K8), and neuronal cells (M3, XI). On the other hand, a recent report found that a pyridinyl imidazole, SB 202190, the specific inhibitor of p38 MAPK, by itself was sufficient to induce apoptosis in T lymphocyte Jurkat cells (N2). Moreover, Th-2-derived cytokine IL-5, the ERK activator and antiapoptotic factor for eosinophils, could also activate p38 MAPK in human eosinophils (BIO). We recently reported that cytokine IL-3, IL-5, and GM-CSF could prolong survival of human eosinophilic leukemic (EoL-1) cells through the transient activation of ERK (W15). On the other hand, activation of p38 MAPK in EoL-1 cells by the NSAID sodium salicylate (NaSal) could lead to apoptosis (W15). We also found that the suppression of ERK using ERK antisense phosphorothioate oligodeoxynucleotides could promote the apoptosis of peripheral blood eosinophils (W16). Moreover, we found that dexamethasone-induced apoptosis and activation of JNK and p38 MAPK activity in eosinophils are regulated by caspases (Z2). 

There are at least three major effector pathways that are activated by neurotrophic factor-Trk receptors. The best-characterized pathway is the extracellular-regulated kinase (ERK) cascade, which is regifiated by activation of Ras, a small membrane-bound G protein. Activation of Ras occurs when activated Trk receptor associates with adaptor proteins and a GTP exchange factor (see Russell and Duman 2002 for details). Ras in turn recruits and activates a serine threonine kinase, Raf, to the membrane resulting in the activation of ERK kinase (also referred to as MEK) and ERK (also known as mitogen activated protein kinase or MAPK). Activation of the Ras-Raf-MEK-ERK cascade can lead to regifiation of many celMar proteins, including ribosomal S6-kinase (RSK). 

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