These data suggest that MIA nocodazole inhibits the activation of p38 in response to extracellular Re charms on de novo protein synthesis, but not by the activity t of p38-mediated de novo protein synthesis. Nocodazole inhibits the activation CYC202 Roscovitine of p38 in response to extracellular Re stimuli by erh Increase of ERK activity suggest t data from previous studies suggest that nocodazole inhibits the activation of p38 in response to extracellular Re stimuli on the activity t p38-independent Independent de novo protein synthesis. Because it was reported that MIAs nnte k The activation of other members of the superfamily of MAPK JNK and ERK, in connection with certain cell stimulating, it is m Possible that a de novo protein synthesis mediated by the activation of other MAPK- away on nocodazole leads to inhibition of activation of p38 in response to extracellular re stimuli.
To test this scenario, we first tested whether nocodazole JNK and ERK activation in Rat-1 cells. As in Fig. 3a indicated, ERK at Thr202 and Tyr204, which is required Barasertib Aurora Kinase inhibitor for the activation of ERK, significantly up regulated nocodazole, w During the phosphorylation of JNK at Thr183 and Tyr185, which is required activation of JNK was barely detectable with nocodazole. Then we analyzed the r The activity of t in the inhibition of ERK activation of p38 in response to extracellular nocodazole Re stimuli with specific ERK inhibitor U0126. U0126 the target ERK activation by inhibiting MEK1 / 2, the upstream Rts MAP2Ks switching ERKactivity induction of MKP of nocodazole, which leads to the inhibition of activation of p38 in response to extracellular stimuli R.
SP600125 Discussion There is increasing evidence that the cytoskeleton in the propagation of signals that gene expression is comparable countries Involved. In addition to the actin network, the cytoplasmic microtubule Another key element in the cytoskeleton, the intracellular Ren signaling brought together. Play among these signaling pathways mediated MAPK signaling pathways an r Insert the key into different cellular Processes undergone such as proliferation, differentiation, survival, death and transformation. Previously mias prior to activation of members of the superfamily of MAPK p38, Including stimulate Lich. However, led to destruction Tion of microtubules MIAs such as taxol and nocodazole on the activation of p38 in response to various extracellular Re chtigt stimuli adversely.
The discrepancy l Sst suggests that the destruction Tion of microtubules, the activation of members of the MAPK superfamily and induces stimulated certain comments and inhibits p38 signaling. Our study best CONFIRMS the hypothesis. In the absence of nocodazole, the TNF or other induce extracellular Re stimuli a rapid and strong activation of p38. However, erh Nocodazole ht fa ERK activity is significant Tw During the destruction Tion of microtubules. ERK activity mediated T is the induction of a big s negative regulator of p38 signaling, N Namely MKP first In the subsequent The challenge of TNF or other extracellular Stimuli will re MKP-1 phosphorylation of p38 by extracellular this Re induced stimuli. In addition, the above data suggest that MKP-1 also ERK phosphorylation decreases by these extracellular Induced re stimuli. Why nocodazole easily obtained Hen the degree of phosphorylation of p38, w While e