The p38/MAPK pathway regulates microtubule polymerization through phosphorylation of MAP4 and Op18 in hypoxic cells
| Autor: | Qiong Zhang, Zhi-Gang Chu, Guang-ping Liang, Yuesheng Huang, Yong-ming Dang, Jian Han, Jiongyu Hu, Hong Yan |
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| Rok vydání: | 2009 |
| Předmět: |
MAPK/ERK pathway
Cell Survival p38 mitogen-activated protein kinases Stathmin Microtubules p38 Mitogen-Activated Protein Kinases Microtubule polymerization Rats Sprague-Dawley Dephosphorylation Cellular and Molecular Neuroscience Microtubule Animals Humans Myocytes Cardiac Anaerobiosis Phosphorylation Hypoxia Microtubule-Associated Protein 4 Molecular Biology Pharmacology biology Chemistry Cell Biology Cell Hypoxia Rats Cell biology biology.protein Molecular Medicine Microtubule-Associated Proteins HeLa Cells |
| Zdroj: | Cellular and Molecular Life Sciences. 67:321-333 |
| ISSN: | 1420-9071 1420-682X |
| Popis: | In both cardiomyocytes and HeLa cells, hypoxia (1% O(2)) quickly leads to microtubule disruption, but little is known about how microtubule dynamics change during the early stages of hypoxia. We demonstrate that microtubule associated protein 4 (MAP4) phosphorylation increases while oncoprotein 18/stathmin (Op18) phosphorylation decreases after hypoxia, but their protein levels do not change. p38/MAPK activity increases quickly after hypoxia concomitant with MAP4 phosphorylation, and the activated p38/MAPK signaling leads to MAP4 phosphorylation and to Op18 dephosphorylation, both of which induce microtubule disruption. We confirmed the interaction between phospho-p38 and MAP4 using immunoprecipitation and found that SB203580, a p38/MAPK inhibitor, increases and MKK6(Glu) overexpression decreases hypoxic cell viability. Our results demonstrate that hypoxia induces microtubule depolymerization and decreased cell viability via the activation of the p38/MAPK signaling pathway and changes the phosphorylation levels of its downstream effectors, MAP4 and Op18. |
| Databáze: | OpenAIRE |
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