JNK phosphorylation

When upstream signaling transduction mechanisms contributing to DON-medi-ated apoptosis were investigated in cloned macrophages, specific inhibition of PKR and Hck additively suppressed DON-induced caspase-3 activity and apoptosis as well as p38, ERK, and JNK phosphorylation.59 Inhibition of PKR and Hck also inhibits DON-induced binding and enzyme activity of p53. 

Huang, C., Rajfur, Z., Borchers, C., et al. 2003. JNK phosphorylates paxillin and regulates cell migration. Nature 424 219-223. 

JNKs induce apoptosis through transcription dependent mechanisms that involve c-jun activation and the induction of pro-apoptotic genes. JNKs phosphorylate Bcl-2 and inactivate it, while activate the pro-apoptotic Bad, Bim and Bmf. JNKs can directly activate Bid independently of the caspase-8. Furthermore, JNKs have a direct action on mitochondria and induce cytochrome c release.143 Figure 19. 

Fig. 3 Mitochondrion-dependent signaling at a early apoptotic stage. The three mayor actions of NO in mitochondria are indicated as reversible binding to complex IV, inhibition of electron transfer at complex III, and oxidation of ubiquinol yielding Oy. The fates of Oy, H2O2, and NO are indicated together with their release into cytosol (the former through VDAC). Modulation of JNK activity (stimulation by H2O2 and inhibition by NO) is indicated. JNK phosphorylates Bcl-2 and Bcl-XL...

Polysaccharide extracted from Hizikia fusiformis (Hf-PS-1) exhibited protective effects against ethanol-induced peptic injury. In in vivo assay, the ethanol group exhibited decrease of total glutathione (GSH) and increase of jun N-terminal kinase (JNK) phosphorylation relative to the control group, whereas levels were significantly increased and decreased, respectively, in the Hf-PS-1 group. Hf-PS-1... 

Moreover, GSH levels were observed to determine if Hf-PS-1 influenced the effect of ethanol metabolism on cellular redox status. Since a Western blot analysis demonstrated the activation of JNK by ethanol, the relationship between ethanol toxicity and JNK activation using the JNK inhibitor SP600125 was examined and found that ethanol treatment decreased GSH levels to 72.72% ( 14.84%) of the control level, but cotreatment with ethanol and either Hf-PS-1 or SP600125 increased GSH levels to 118.18% ( 10.49%) or 95.45% ( 9.09%), respectively, of the control level (Pig. 11.14). These results suggest that Hf-PS-1 protects against ethanol-induced damage by inhibiting JNK phosphorylation and that JNK plays an important role in ethanol-induced toxicity. 

It appears hkely that in cells other than hepatic stellate cells, 4-HNE activates JNKs through phosphorylation rather than direct binding. Uchida et al., dranonstrat-ing a rapid increase in JNK phosphorylation in rat liver epithelial RL34 cells, reached this conclusion." These authors also reported a mild effect of the aldehyde on ERK activity, while Ruef et al. showed a significant activation of ERKl and ERK2 in 4-HNE treated rat aortic smooth muscle cells." The aldehyde, at concentrations effective on JNKs, also markedly activates novel PKC isoforms, in particular, PKC beta in hepatocytes." ... 

Lei, K, and Davis, R. J. (2003). JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc. Natl. Acad. Sd. USA 100, 2432-2437. 

Jang S, Kelley KW, Johnson RW (2008) Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc Natl Acad Sci USA 105(21) 7534-7539. doi 10.1073/pnas.0802865105,0802865105 [pii]... 

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