Inhibition by Rho-kinase and protein kinase C of myosin phosphatase is involved in thrombin-induced shape change of megakaryocytic leukemia cell line UT-7/TPO

Yazaki, Akira; Tamaru, Satoshi; Sasaki, Yasuharu; Komatsu, Nobuo; Wada, Hideo; Shiku, Hiroshi; Nishikawa, Masakatsu

doi:10.1016/j.cellsig.2004.07.009

Cited by 9 publications

(11 citation statements)

References 24 publications

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“…This prolonged elevated permeability is attributed to the activation of the small Rho GTPase and Rho kinase [54,55]. It has been found that Rho GTPase activation can be observed after 2 min and the elevated activation is maintained up to 60 min after thrombin stimulation, and the time course of Rho GTPase activation correlates well with the time course of MLC activation increase by experiment observation [54].…”

Section: Resultsmentioning

confidence: 99%

An Integrated Mathematical Model of Thrombin-, Histamine-and VEGF-Mediated Signalling in Endothelial Permeability

et al. 2011

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BackgroundEndothelial permeability is involved in injury, inflammation, diabetes and cancer. It is partly regulated by the thrombin-, histamine-, and VEGF-mediated myosin-light-chain (MLC) activation pathways. While these pathways have been investigated, questions such as temporal effects and the dynamics of multi-mediator regulation remain to be fully studied. Mathematical modeling of these pathways facilitates such studies. Based on the published ordinary differential equation models of the pathway components, we developed an integrated model of thrombin-, histamine-, and VEGF-mediated MLC activation pathways.ResultsOur model was validated against experimental data for calcium release and thrombin-, histamine-, and VEGF-mediated MLC activation. The simulated effects of PAR-1, Rho GTPase, ROCK, VEGF and VEGFR2 over-expression on MLC activation, and the collective modulation by thrombin and histamine are consistent with experimental findings. Our model was used to predict enhanced MLC activation by CPI-17 over-expression and by synergistic action of thrombin and VEGF at low mediator levels. These may have impact in endothelial permeability and metastasis in cancer patients with blood coagulation.ConclusionOur model was validated against a number of experimental findings and the observed synergistic effects of low concentrations of thrombin and histamine in mediating the activation of MLC. It can be used to predict the effects of altered pathway components, collective actions of multiple mediators and the potential impact to various diseases. Similar to the published models of other pathways, our model can potentially be used to identify important disease genes through sensitivity analysis of signalling components.

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Section: Resultsmentioning

confidence: 99%

An Integrated Mathematical Model of Thrombin-, Histamine-and VEGF-Mediated Signalling in Endothelial Permeability

et al. 2011

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“…These results are consistent with the recent experimental finding that CPI‐17 was uncorrelated with the sustained MYPT1 phosphorylation (Murthy et al . 2003; Yazaki et al . 2005), and that thrombin‐dependent CPI‐17 phosphorylation was not observed in some cell lines (Kolosova et al .…”

Section: Resultsmentioning

confidence: 99%

Ca²⁺‐independent phospholipase A2‐dependent sustained Rho‐kinase activation exhibits all‐or‐none response

et al. 2006

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“…Protein kinase C is a multivariety protein in cells of the body. It regulates many cellular functions by manipulating other enzyme activities 35 . It is reported that inhibition of PKC results in amelioration of existing inflammation 34 .…”

Section: Discussionmentioning

confidence: 99%

Investigation into the signal transduction pathway via which heat stress impairs intestinal epithelial barrier function

Yang

Zheng

2007

J of Gastro and Hepatol

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Inhibition by Rho-kinase and protein kinase C of myosin phosphatase is involved in thrombin-induced shape change of megakaryocytic leukemia cell line UT-7/TPO

Cited by 9 publications

References 24 publications

An Integrated Mathematical Model of Thrombin-, Histamine-and VEGF-Mediated Signalling in Endothelial Permeability

An Integrated Mathematical Model of Thrombin-, Histamine-and VEGF-Mediated Signalling in Endothelial Permeability

Ca²⁺‐independent phospholipase A2‐dependent sustained Rho‐kinase activation exhibits all‐or‐none response

Investigation into the signal transduction pathway via which heat stress impairs intestinal epithelial barrier function

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Inhibition by Rho-kinase and protein kinase C of myosin phosphatase is involved in thrombin-induced shape change of megakaryocytic leukemia cell line UT-7/TPO

Cited by 9 publications

References 24 publications

An Integrated Mathematical Model of Thrombin-, Histamine-and VEGF-Mediated Signalling in Endothelial Permeability

An Integrated Mathematical Model of Thrombin-, Histamine-and VEGF-Mediated Signalling in Endothelial Permeability

Ca2+‐independent phospholipase A2‐dependent sustained Rho‐kinase activation exhibits all‐or‐none response

Investigation into the signal transduction pathway via which heat stress impairs intestinal epithelial barrier function

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Ca²⁺‐independent phospholipase A2‐dependent sustained Rho‐kinase activation exhibits all‐or‐none response