The p38 MAPK signaling pathway has been proposed as a critical mediator of the therapeutic effect of several antitumor agents, including cisplatin. Here, we found that sensitivity to cisplatin, in a system of 7 non-small cell lung carcinoma derived cell lines, correlated with high levels of MKK6 and marked activation of p38 MAPK. However, knockdown of MKK6 modified neither the response to cispl...

Exogenous fibroblast growth factor 1 (FGF1) signals through activation of transmembrane FGF receptors (FGFRs) but may also regulate cellular processes after translocation to the cytosol and nucleus of target cells. Translocation of FGF1 occurs across the limiting membrane of intracellular vesicles and is a regulated process that depends on the C-terminal tail of the FGFR. Here, we report that t...

Recent evidence suggests p38 mitogen-activated protein kinase (MAPK) signal transduction plays an important role in the pathogenesis of progressive renal disease. Using dynamic contrast enhanced magnetic resonance imaging (MRI), we evaluated chronic treatment with a p38 MAPK inhibitor, trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl-methoxypyridimidin-4-yl)imidazole (SB-239063), on renal functi...

p38 mitogen-activated protein kinase (MAPK) signaling promotes diabetic kidney injury. Apoptosis signal-regulating kinase (ASK)1 is one of the upstream kinases in the p38 MAPK-signaling pathway, which is activated by inflammation and oxidative stress, suggesting a possible role for ASK1 in diabetic nephropathy. In this study, we examined whether a selective ASK1 inhibitor can prevent the induct...

We investigated the ability of phenylephrine (PE), an alpha-adrenergic agonist and promoter of hypertrophic growth in the ventricular myocyte, to activate the three best-characterized mitogen-activated protein kinase (MAPK) subfamilies, namely p38-MAPKs, SAPKs/JNKs (i.e. stress-activated protein kinases/c-Jun N-terminal kinases) and ERKs (extracellularly responsive kinases), in perfused contrac...

Thrombin, the terminal serine protease in the coagulation cascade, is a proinflammatory molecule in vivo and induces endothelial activation in vitro. The cellular signaling mechanisms involved in this function are unknown. The role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in thrombin-induced chemokine production was studied. Phosphorylation of both p38 MAPK and its s...

Li, Zhihe, Jing Ying Ma, Irene Kerr, Sarvajit Chakravarty, Sundeep Dugar, George Schreiner, and Andrew A. Protter. Selective inhibition of p38 MAPK improves cardiac function and reduces myocardial apoptosis in rat model of myocardial injury. Am J Physiol Heart Circ Physiol 291: H1972–H1977, 2006. First published June 2, 2006; doi:10.1152/ajpheart.00043.2006.—p38 MAPK is activated during heart d...

BACKGROUND/AIM Protein-bound polysaccharide-K (PSK) is extracted from Coriolus versicolor (CM101) and is clinically used in combination therapy for gastrointestinal cancer and small-cell lung carcinoma. We have previously demonstrated that PSK induces apoptosis and inhibites proliferation of promyelomonocytic leukemia HL-60 cells, but the signaling pathway for this action remains to be elucidat...

We investigated the involvement of mitogen-activated protein kinases (MAPKs) in the maturation of CD83(-) dendritic cells (DC) derived from human blood monocytes. Maturating agents such as LPS and TNF-alpha induced the phosphorylation of members of the three families of MAPK (extracellular signal-regulated kinase l/2, p46/54 c-Jun N-terminal kinase, and p38 MAPK). SB203580, an inhibitor of the ...