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Hypoxia modulates the expression of leucine zipper-positive MYPT1 and its interaction with protein kinase G and Rho kinases in pulmonary arterial smooth muscle cells.

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Title: Hypoxia modulates the expression of leucine zipper-positive MYPT1 and its interaction with protein kinase G and Rho kinases in pulmonary arterial smooth muscle cells.
Author(s): Singh, Dev K.; Sarkar, Joy; Raghavan, Aarti; Reddy, Sekhar P.; Raj, J. Usha
Subject(s): hypoxia-induced pulmonary hypertension signal transduction cGMP pulmonary vasoconstriction
Abstract: We have shown previously that acute hypoxia downregulates protein kinase G (PKG) expression and activity in ovine fetal pulmonary vessels and pulmonary arterial smooth muscle cells (SMC). Here, we report that acute hypoxia also reduces the expression of leucinezipper-positive MYPT1 (LZ(+)MYPT1), a subunit of myosin light chain (MLC) phosphatase, in ovine fetal pulmonary arterial SMC. We found that in hypoxia, there is greater interaction between LZ(+) MYPT1 and RhoA and Rho kinase 1 (ROCK1)/Rho kinase 2 (ROCK2) and decreased interaction between LZ(+) MYPT1 and PKG, resulting in increased MLC(20) phosphorylation, a higher pMLC(20)/MLC(20) ratio and SMC contraction. In normoxic SMC PKG overexpression, LZ(+) MYPT1 expression is upregulated while PKG knockdown had an opposite effect. LZ(+) MYPT1 overexpression enhanced the interaction between PKG and LZ(+) MYPT1. Overexpression of a mutant LZ(-) MYPT1 isoform in SMC mimicked the effects of acute hypoxia and decreased pMLC(20)/MLC(20) ratio. Collectively, our data suggest that hypoxia downregulates LZ(+) MYPT1 expression by suppressing PKG levels, reduces the interaction of LZ(+) MYPT1 with PKG and promotes LZ(+) MYPT1 interaction with RhoA or ROCK1/ROCK2, thereby promoting pulmonary arterial SMC contraction.
Issue Date: 2011-10
Publisher: Medknow Publications
Citation Info: Singh DK, Sarkar J, Raghavan A, Reddy SP, Raj JU. Hypoxia modulates the expression of leucine zipper-positive MYPT1 and its interaction with protein kinase G and Rho kinases in pulmonary arterial smooth muscle cells. Pulmonary Circulation. 2011 Oct;1(4):487-98. DOI: 10.4103/2045-8932.93548
Type: Article
Description: This is a copy of an article published in the Pulmonary Circulation © 2011 Medknow Publications. DOI: 10.4103/2045-8932.93548
URI: http://hdl.handle.net/10027/8721
ISSN: 2045-8940
Date Available in INDIGO: 2012-10-02
 

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