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Fractional activation of myosin light chain kinase is sufficient for robust smooth muscle contraction
Author(s) -
Gao Ning,
Huang Jian,
He WeiQi,
Zhu Minsheng,
Kamm Kristine E.,
Stull James T.
Publication year - 2011
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.25.1_supplement.1115.8
Subject(s) - myosin light chain kinase , myosin , contraction (grammar) , immunoglobulin light chain , biophysics , rho associated protein kinase , muscle contraction , chemistry , myh7 , kinase , microbiology and biotechnology , medicine , biology , biochemistry , genetics , antibody
Ca2+/calmodulin‐dependent myosin light chain kinase (MLCK) is necessary and sufficient for phosphorylation of myosin regulatory light chain (RLC) for smooth muscle contraction (He et al., 2008; Zhang et al., 2010). However, it was noted that a biosensor MLCK was activated only 25% for maximal agonist‐induced contraction (Isotani et al., 2004). We therefore used a tamoxifen‐activated and smooth muscle‐specific inactivation of MLCK expression in adult mice to determine if a small fraction of MLCK was sufficient for RLC phosphorylation and contraction. An 80% decrease in MLCK content in bladder smooth muscle strips resulted in a 60% and 50% decrease in maximal RLC phosphorylation and contractile responses to KCl, respectively, but only a 20% decrease in maximal responses to 10 uM carbachol (CCh). Phosphorylation of the regulatory subunit (MYPT1) of myosin light chain phosphatase (MLCP) inhibits its activity and thus, enhances RLC phosphorylation. MLCK knockdown did not change MYPT1 Thr695 and Thr850 phosphorylation responses to CCh, but did enhance MLCP inhibitor protein CPI‐17 phosphorylation. Thus, activation of a small fraction of MLCK along with MLCP inhibition may be sufficient for robust RLC phosphorylation and contractile responses in smooth muscles. Supported by HL26043.