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dc.contributor.authorSingh, Dev K.
dc.contributor.authorSarkar, Joy
dc.contributor.authorRaghavan, Aarti
dc.contributor.authorreddy, Sekhar P.
dc.contributor.authorRaj, J. Usha
dc.date.accessioned2013-12-03T20:47:49Z
dc.date.available2013-12-03T20:47:49Z
dc.date.issued2011-10
dc.identifier.bibliographicCitationSingh 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;1(4):487-498. DOI: 10.4103/2045-8932.93548en_US
dc.identifier.issn2045-8940
dc.identifier.urihttp://hdl.handle.net/10027/10746
dc.descriptionThe original version is available through Medknow Publications at DOI: 10.4103/2045-8932.93548.en_US
dc.description.abstractWe 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.en_US
dc.description.sponsorshipNIH/NHLBI Grants HL-059435 and HL-075187en_US
dc.language.isoen_USen_US
dc.publisherMedknow Publicationsen_US
dc.subjectsignal transuctionen_US
dc.subjectpulmonary vasoconstrictionen_US
dc.subjectcGMPen_US
dc.titleHypoxia modulates the expression of leucine zipper-positive MYPT1 and its interaction with protein kinase G and Rho kinases in pulmonary arterial smooth muscle cellsen_US
dc.typeArticleen_US


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