Regulation of Drosophila p38 activation by specific MAP2 kinase and MAP3 kinase in response to different stimuli.
The p38 mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in cellular responses to inflammatory stimuli and environmental stress. Activation of p38 is mediated through phosphorylation by upstream MAPKK, which in turn is activated by MAPKKK. However, the mechanism of how different upstream MAP2Ks and MAP3Ks specifically contribute to p38 activation in response to different stimuli is still not clearly understood. By using double-stranded RNA-mediated interference (RNAi) in Drosophila cells, we demonstrate that D-MKK3 is a major MAP2K responsible for D-p38 activation by UV, heat shock, NaCl or peptiodglycan (PGN). Stimulation of UV and PGN activates D-p38 through D-MEKK1, heat shock-induced activation of D-p38 signals through both D-MEKK1 and D-ASK1. On the other hand, maximal activation of D-p38 by NaCl requires the expression of four MAP3Ks.
Zhuang
Zi-Heng
ZH
Signal Transduction Lab of Institute of Health Sciences, Shanghai Institutes for Biological Sciences [corrected] Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine [corrected] PR China.
Zhou
Yuan
Y
Yu
Ming-Can
MC
Silverman
Neal
N
Ge
Bao-Xue
BX
D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D006358:Hot Temperature; D048369:MAP Kinase Kinase 1 / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D048370:MAP Kinase Kinase 2 / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D048371:MAP Kinase Kinase 3 / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010457:Peptidoglycan / Q000494:pharmacology; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000494:pharmacology; D015398:Signal Transduction; D012965:Sodium Chloride / Q000494:pharmacology; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects
D010457:Peptidoglycan; D012330:RNA, Double-Stranded; D012965:Sodium Chloride; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D048371:MAP Kinase Kinase 3