Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incorporation of 32P into telokin, a smooth muscle-specific, 17-18-kDa, acidic (pI 4.2-4.4) protein, was increased by forskolin (20 microM) in intact rabbit ileum smooth muscle (ileum) and by 8-bromo-cyclic GMP (100 microM) in alpha-toxin-permeabilized ileum. Native telokin (5-20 microM), purified from turkey gizzard, and recombinant rabbit telokin, expressed in Escherichia coli and purified to >90% purity, induced dose-dependent relaxation, associated with a significant decrease in regulatory myosin light chain phosphorylation, without affecting the rate of thiophosphorylation of regulatory myosin light chain of ileum permeabilized with 0.1% Triton X-100. Endogenous telokin was lost from ileum during prolonged permeabilization (>20 min) with 0.1% Triton X-100, and the time course of loss was correlated with the loss of 8-bromo-cyclic GMP-induced calcium desensitization. Recombinant and native gizzard telokins were phosphorylated, in vitro, by the catalytic subunit of cAMP-dependent protein kinase, cGMP-dependent protein kinase, and p42/44 mitogen-activated protein kinase; the recombinant protein was also phosphorylated by calmodulin-dependent protein kinase II. Exogenous cGMP-dependent protein kinase (0.5 microM) activated by 8-bromo-cyclic GMP (50 microM) phosphorylated recombinant telokin (10 microM) when added concurrently to ileum depleted of its endogenous telokin, and their relaxant effects were mutually potentiated. Forskolin (20 microM) also increased phosphorylation of telokin in intact ileum. We conclude that telokin induces calcium desensitization in smooth muscle by enhancing myosin light chain phosphatase activity, and cGMP- and/or cAMP-dependent phosphorylation of telokin up-regulates its relaxant effect.
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PMID:Acceleration of myosin light chain dephosphorylation and relaxation of smooth muscle by telokin. Synergism with cyclic nucleotide-activated kinase. 955 31

Telokin, a 17 kDa smooth muscle specific protein, consists of the C-terminal domain of MLCK, is phosphorylated by PKA and PKG at Ser13 in vivo (Wu et al. (1998) J Biol Chem 273: 11362-11369; Walker et al. (2001) J. Biol Chem 276: 24519-24524) and is proposed to induce Ca2+-desensitization through activation of myosin phosphatase (Wu et al. (1998) J. Biol Chem 273: 11362-11369). Telokin is reported to be highly expressed in phasic with only trace amounts in tonic smooth muscle. In alpha-toxin permeabilized femoral artery, 5 microM 8-Br-cGMP induced a two-fold increase in telokin phosphorylation and a maximal 30% relaxation of Ca2+-activated force compared to a 90% relaxation in phasic ileum muscle consistent with the relative amounts of telokin expressed in ileum, 27+/-4.6 microM SEM compared to 6+/-1.7 microM SEM, in femoral artery. Recombinant Wt telokin and the phospho-telokin mutant, S13D relaxed telokin-depleted femoral artery, by 38+/-8% SEM and 60+/-20% SEM, respectively. 8-Br-cGMP increased the rate and decreased the amplitude of force development initiated by photolysis of caged ATP in alpha-toxin permeabilized ileum and femoral artery smooth muscle, consistent with a cGMP-induced increase in phosphatase activity. Similarly, in telokin depleted ileum, recombinant S13D mutant telokin significantly increased the rate (0.08+/-0.01 s-1 vs. 014+/-0.02 s-1) and decreased force amplitude. In conclusion, our data support a role for telokin in cyclic nucleotide-induced relaxation of not only phasic, but also tonic smooth muscle and that this relaxation is mediated by activation of myosin phosphatase activity leading to a decrease in myosin light chain phosphorylation.
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PMID:Telokin mediates Ca2+-desensitization through activation of myosin phosphatase in phasic and tonic smooth muscle. 1575 Aug 50