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J Biol Chem. 2002 Nov 8;277(45):42596-602. Epub 2002 Aug 28.

Cytoskeletal changes in hypoxic pulmonary endothelial cells are dependent on MAPK-activated protein kinase MK2.

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  • 1Pulmonary and Critical Care Division, Department of Medicine/Tupper Research Institute, Tufts-New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Abstract

Exposure to hypoxia causes structural changes in the endothelial cell layer that alter its permeability and its interaction with leukocytes and platelets. One of the well characterized cytoskeletal changes in response to stress involves the reorganization of the actin cytoskeleton and the formation of stress fibers. This report describes cytoskeletal changes in pulmonary microvascular endothelial cells in response to hypoxia and potential mechanisms involved in this process. The hypoxia-induced actin redistribution appears to be mediated by components downstream of MAPK p38, which is activated in pulmonary endothelial cells in response to hypoxia. Our results indicate that kinase MK2, which is a substrate of p38, becomes activated by hypoxia, leading to the phosphorylation of one of its substrates, HSP27. Because HSP27 phosphorylation is known to alter actin distribution in response to other stimuli, we postulate that it also causes the actin redistribution observed in hypoxia. This notion is supported by the observations that similar actin redistribution occurs in cells overexpressing constitutively active MK2 or phosphomimicking HSP27 mutant. Overexpressing dominant negative MK2 blocks the effects of hypoxia on the actin cytoskeleton. Taken together these results indicate that hypoxia stimulates the p38-MK2-HSP27 pathway leading to significant alteration in the actin cytoskeleton.

PMID:
12202485
[PubMed - indexed for MEDLINE]
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