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Phosphorylation of CPI‐17 and MYPT in rabbit bladder smooth muscle: Role of PKC, Rho kinase, or both
Author(s) -
Wang Tanchun,
Kendig Derek M.,
Smolock Elaine M.,
Moreland Robert S.
Publication year - 2007
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.21.6.a1300-d
Subject(s) - phosphorylation , protein kinase c , dephosphorylation , myosin light chain phosphatase , carbachol , myosin light chain kinase , microbiology and biotechnology , biology , bisindolylmaleimide , rho associated protein kinase , phosphatase , endocrinology , stimulation
Smooth muscle is regulated by phosphorylation of the myosin light chain (MLC) catalyzed by MLC kinase and dephosphorylation catalyzed by MLC phosphatase (MLCP). Inhibition of the MLCP following agonist stimulation results in a net increase in MLC phosphorylation due to PKC catalyzed CPI‐17 phosphorylation or Rho kinase (ROK) catalyzed phosphorylation of a phosphatase subunit (MYPT). This study was designed to investigate if PKC and ROK inhibit MLCP by two distinct pathways or if there is cross‐talk in bladder smooth muscle. This goal was pursued by measuring contraction of rabbit bladder smooth muscle in response to carbachol or phorbol dibutyrate (PDBu) in the absence and presence of inhibitors of PKC (Bisindolylmaleimide‐1) or ROK (H‐1152). Inhibition of PKC and ROK depressed both carbachol and PDBu induced contractions. PKC inhibition decreases contraction mainly through the inhibition of CPI‐17 phosphorylation and to a lesser degree by inhibition of MYPT phosphorylation at both Thr 696 and Thr 850 . ROK inhibition decreases basal levels of MYPT phosphorylation, predominantly at Thr 850 which suggests a role for a constitutively active ROK. We propose that PKC modulates contraction directly by phosphorylation of CPI‐17 and indirectly by activation of ROK resulting in an increase in MYPT phosphorylation. ROK on the other hand only acts via MPYT phosphorylation in bladder smooth muscle.