INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

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

Show simple item record

Bookmark or cite this item: http://hdl.handle.net/10027/8361

Files in this item

File Description Format
PDF PulmCirc14487-4852864_132848.pdf (2MB) (no description provided) PDF
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
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 MLC20 phosphorylation, a higher pMLC20/MLC20 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 pMLC20/MLC20 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
Publisher: Medknow Publications
Citation Info: Singh, D. K., Sarkar, J., Raghavan, A., Reddy, S. P., & Raj, J. U. 2011. 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, 1(4): 487-498. doi: 10.4103/2045-8932.93548
Type: Article
Description: The original version is available through Medknow Publications at doi: 10.4103/2045-8932.93548
URI: http://hdl.handle.net/10027/8361
ISSN: 2045-8932
Date Available in INDIGO: 2012-06-20
 

This item appears in the following Collection(s)

Show simple item record

Statistics

Country Code Views
United States of America 287
China 76
Russian Federation 17
Germany 11
United Kingdom 11

Browse

My Account

Information

Access Key