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Possible involvement of the novel CPI‐17 protein in protein kinase C signal transduction of rabbit arterial smooth muscle
Author(s) -
Li L.,
Eto M.,
Lee M. R.,
Morita F.,
Yazawa M.,
Kitazawa T.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.871bp.x
Subject(s) - phosphatase , dephosphorylation , phosphorylation , protein kinase c , myosin light chain phosphatase , myosin light chain kinase , kinase , chemistry , signal transduction , protein kinase a , microbiology and biotechnology , protein phosphorylation , biochemistry , biology
1 CPI‐17 has recently been identified as a novel protein in vascular smooth muscle. In vitro , its phosphorylation and thiophosphorylation by protein kinase C (PKC) specifically inhibits the type 1 class of protein phosphatases, including myosin light chain (MLC) phosphatase. 2 Both of the phosphorylated CPI‐17 states dose‐dependently potentiated submaximal contractions at constant [Ca 2+ ] in β‐escin‐permeabilized and Triton X‐100‐demembranated arterial smooth muscle, but produced no effect in intact and less intensely permeabilized (α‐toxin) tissue. Thiophosphorylated CPI‐17 (tp‐CPI) induced large contractions even under Ca 2+ ‐free conditions and decreased Ca 2+ EC 50 by more than an order of magnitude. Unphosphorylated CPI‐17 produced minimal but significant effects. 3 tp‐CPI substantially increased the steady‐state MLC phosphorylation to Ca 2+ ratios in β‐escin preparations. 4 tp‐CPI affected the kinetics of contraction and relaxation and of MLC phosphorylation and dephosphorylation in such a manner that indicates its major physiological effect is to inhibit MLC phosphatase. 5 Results from use of specific inhibitors in concurrence with tp‐CPI repudiate the involvement of general G proteins, rho A or PKC itself in the Ca 2+ sensitization by tp‐CPI. 6 Our results indicate that phosphorylation of CPI‐17 by PKC stimulates binding of CPI‐17 to and subsequent inhibition of MLC phosphatase. This implies that CPI‐17 accounts largely for the heretofore unknown signalling pathway between PKC and inhibited MLC phosphatase.