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MYPT1 isoform expression is regulated by p42/44 signaling
Author(s) -
Brozovich Nikolas J,
Hawes Grescin,
Yuen Samantha,
Ogut Ozgur,
Brozovich Frank V
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.870.3
Subject(s) - myosin light chain phosphatase , mapk/erk pathway , microbiology and biotechnology , phosphatase , phosphorylation , protein phosphatase 1 , myosin light chain kinase , signal transduction , downregulation and upregulation , myosin , stimulation , chemistry , biology , endocrinology , biochemistry , gene
During NO mediated vasodilatation, PKG activates myosin light chain (MLC) phosphatase to reduce MLC phosphorylation and force. MLC phosphatase is a trimeric enzyme consisting of a catalytic, myosin targeting (MYPT1) and 20 kDa subunits. Alternative mRNA splicing produces four MYPT1 isoforms, which differ by the presence or absence of central insert (CI) and a carboxy‐terminal luecine zipper (LZ). PKG mediated activation of MLC phosphatase requires the expression of a LZ+ MYPT1 isoform, and during heart failure, there is an activation of p42/44 MAPK signaling and a decrease in LZ+ MYPT1 expression. We examined p42/44 MAPK signaling and LZ+ MYPT1 expression during angiotensin II (AngII) stimulation of cultured smooth muscle cells (SMCs). AngII resulted in a time dependent activation of p42/44 MAPK and a decrease in LZ+ MYPT1 expression. However pretreatment of the SMCs with a MEK inhibitor (PD98059) blocked the AngII induced activation of p42/44 MAPK and decrease of LZ+ MYPT1 expression. These results demonstrate that LZ+ MYPT1 expression is regulated by a p42/44 MAPK signaling pathway. During heart failure, treatment with either ACE inhibitors or AngII receptor blockers will prevent the activation of p42/44 MAPK and the resulting decrease in LZ+ MYPT1 expression to preserve the sensitivity of vascular smooth muscle to NO mediated vasodilatation.