The p38/MAPK pathway regulates microtubule polymerization through phosphorylation of MAP4 and Op18 in hypoxic cells.

Abstract

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.

• Authors: Jiong-Yu Hu, Zhi-Gang Chu, Jian Han, Yong-ming Dang, Hong Yan, Qiong Zhang, Guang-ping Liang, Yue-Sheng Huang
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 67 Issue 2 Pg. 321-33 (Jan 2010) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 19915797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Microtubule-Associated Proteins
• Stathmin
• p38 Mitogen-Activated Protein Kinases

Topics

• Anaerobiosis
• Animals
• Cell Hypoxia
• Cell Survival
• HeLa Cells
• Humans
• Hypoxia (metabolism)
• Microtubule-Associated Proteins (metabolism)
• Microtubules (enzymology, metabolism)
• Myocytes, Cardiac (metabolism)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Stathmin (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)