Zhuang, Zi-HengZhou, YuanYu, Ming-CanSilverman, NealGe, Bao-Xue2022-08-232022-08-232005-07-152008-12-19Cell Signal. 2006 Apr;18(4):441-8. Epub 2005 Jul 12. <a href="http://dx.doi.org/10.1016/j.cellsig.2005.05.013">Link to article on publisher's site</a>0898-6568 (Print)10.1016/j.cellsig.2005.05.01316014325https://hdl.handle.net/20.500.14038/35256The 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.en-USAnimalsCell LineDrosophilaHeatMAP Kinase Kinase 1MAP Kinase Kinase 2MAP Kinase Kinase 3MAP Kinase Kinase Kinase 5MAP Kinase Signaling SystemPeptidoglycanRNA InterferenceRNA, Double-StrandedSignal TransductionSodium ChlorideUltraviolet Raysp38 Mitogen-Activated Protein KinaseseffectsImmunology and Infectious DiseaseJournal Articlehttps://escholarship.umassmed.edu/infdis_pp/9684320infdis_pp/9