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Protein Kinase Signalling Pathway (protein + kinase_signalling_pathway)

Distribution by Scientific Domains
Life Sciences71%

Kinds of Protein Kinase Signalling Pathway

  • mitogen-activated protein kinase signalling pathway
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    Selected Abstracts

    Role of intracellular Ca2+ and calmodulin/MAP kinase kinase/extracellular signal-regulated protein kinase signalling pathway in the mitogenic and antimitogenic effect of nitric oxide in glia- and neurone-derived cell lines

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006
    Antonella Meini
    Abstract To elucidate the mechanism of cell growth regulation by nitric oxide (NO) and the role played in it by Ca2+, we studied the relationship among intracellular Ca2+ concentration ([Ca2+]i), mitogen-activated protein kinases [extracellular signal-regulated protein kinase (ERK)] and proliferation in cell lines exposed to different levels of NO. Data showed that NO released by low [(z)-1-[2-aminiethyl]-N-[2-ammonioethyl]amino]diazen-1-ium-1,2diolate (DETA/NO) concentrations (10 µm) determined a gradual, moderate elevation in [Ca2+]i (46.8 ± 7.2% over controls) which paralleled activation of ERK and potentiation of cell division. Functionally blocking Ca2+ or inhibiting calmodulin or MAP kinase kinase activities prevented ERK activation and antagonized the mitogenic effect of NO. Experimental conditions favouring Ca2+ entry into cells led to increased [Ca2+]i (189.5 ± 4.8%), ERK activation and cell division. NO potentiated the Ca2+ elevation (358 ± 16.8%) and ERK activation leading to expression of p21Cip1 and inhibition of cell proliferation. Furthermore, functionally blocking Ca2+ down-regulated ERK activation and reversed the antiproliferative effect of NO. Both the mitogenic and antimitogenic responses induced by NO were mimicked by a cGMP analogue whereas they were completely antagonized by selective cGMP inhibitors. These results demonstrate for the first time that regulation of cell proliferation by low NO levels is cGMP dependent and occurs via the Ca2+/calmodulin/MAP kinase kinase/ERK pathway. In this effect the amplitude of Ca2+ signalling determines the specificity of the proliferative response to NO possibly by modulating the strength of ERK activation. In contrast to the low level, the high levels (50,300 µm) of DETA/NO negatively regulated cell proliferation via a Ca2+ -independent mechanism. [source]

    RNA interference targeting the platelet-derived growth factor receptor , subunit ameliorates experimental hepatic fibrosis in rats

    LIVER INTERNATIONAL, Issue 10 2008
    Si-Wen Chen
    Abstract Background/Aims: Platelet-derived growth factor (PDGF) is the strongest stimulator of the proliferation of hepatic stellate cells (HSCs). PDGF receptor , subunit (PDGFR-,) is acquired on HSCs proliferation induced by PDGF. In this study, we aim to investigate the effect of PDGFR-, small interference RNA (siRNA) on experimental hepatic fibrosis. Methods: We constructed a PDGFR-, siRNA expression plasmid and investigated its effect on the activation of HSCs. Bromodeoxyuridine incorporation was performed to investigate the effect of PDGFR-, siRNA on HSCs proliferation. A hydrodynamics-based transfection method was used to deliver PDGFR-, siRNA to rats with hepatic fibrosis. The distribution of transgenes in the liver was observed by immunofluorescence. The antifibrogenic effect of PDGFR-, siRNA was investigated pathologically. Results: Platelet-derived growth factor receptor-, subunit siRNA could significantly downregulate PDGFR-, expression, suppress HSCs activation, block the mitogen-activated protein kinase signalling pathway and inhibit HSCs proliferation in vitro. PDGFR-, siRNA expression plasmid could be delivered into activated HSCs by the hydrodynamics-based transfection method, and remarkably improve the liver function of the rat model induced by dimethylnitrosamine and bile duct ligation. Furthermore, the progression of fibrosis in the liver was significantly suppressed by PDGFR-, siRNA in both animal models. Conclusions: Platelet-derived growth factor receptor-, subunit siRNA may be presented as an effective antifibrogenic gene therapeutic method for hepatic fibrosis. [source]

    Hybrid Lethality in Interspecific F1 Hybrid Nicotiana gossei×N. tabacum Involves a MAP-Kinases Signalling Cascade

    PLANT BIOLOGY, Issue 3 2007
    M. Mino
    Abstract: A cultured cell line, GTH4 (Nicotiana gossei Domin ×N. tabacum L.), which exhibits hybrid lethality, died at 26 °C, but not at 37 °C. Pharmacological experiments using inhibitors of protein phosphatases and protein kinases indicated the involvement of a protein kinase signalling pathway in the cell death process. Immunoblot analysis revealed that salicylic acid-induced protein kinase (SIPK) was phosphorylated soon after the shift in temperature from 37 °C to 26 °C. Cultured cells of the hybrid of N. gossei× transgenic N. tabacum harboring a steroid (dexamethasone; DEX)-inducible NtMEK2DD or NtMEK2KR, constitutively active and inactive forms of NtMEK2, respectively, were established. Induction of NtMEK2DD by DEX in the hybrid cells induced the activation of SIPK, the generation of hydrogen peroxide (H2O2), and cell death at 37 °C. The activation of SIPK, generation of H2O2, and cell death at 26 °C were compromised by DEX treatment in hybrid cells harbouring NtMEK2KR. This study provides evidence for the involvement of MAPK signalling in the regulation of cell death in hybrids. [source]

    Structural analysis of an MK2,inhibitor complex: insight into the regulation of the secondary structure of the Gly-rich loop by TEI-I01800

    ACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2010
    Aiko Fujino
    Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK2) is a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway and plays an important role in inflammatory diseases. The crystal structure of the complex of human MK2 (residues 41,364) with the potent MK2 inhibitor TEI-I01800 (pKi = 6.9) was determined at 2.9,Å resolution. The MK2 structure in the MK2,TEI-I01800 complex is composed of two domains, as observed for other Ser/Thr kinases; however, the Gly-rich loop in the N-terminal domain forms an ,-helix structure and not a ,-sheet. TEI-I01800 binds to the ATP-binding site as well as near the substrate-binding site of MK2. Both TEI-I01800 molecules have a nonplanar conformation that differs from those of other MK2 inhibitors deposited in the Protein Data Bank. The MK2,TEI-I01800 complex structure is the first active MK2 with an ,-helical Gly-rich loop and TEI-I01800 regulates the secondary structure of the Gly-rich loop. [source]

    Trophic factors attenuate nitric oxide mediated neuronal and axonal injury in vitro: roles and interactions of mitogen-activated protein kinase signalling pathways

    JOURNAL OF NEUROCHEMISTRY, Issue 6 2005
    Alastair Wilkins
    Abstract Inflammation in the central nervous system occurs in diseases such as multiple sclerosis and leads to axon dysfunction and destruction. Both in vitro and in vivo observations have suggested an important role for nitric oxide (NO) in mediating inflammatory axonopathy. The purposes of this study were to model inflammatory axonopathy in vitro and identify modulators of the process. Rat cortical neurones were cultured and exposed to an NO-donor plus potential protective factors. Cultures were then assessed for neuronal survival, axon survival and markers of intracellular signalling pathways. The NO-donor produced dose-dependent neuronal loss and a large degree of axon destruction. Oligodendrocyte conditioned medium (OCM) and insulin-like growth factor type-1 (IGF-1), but not glial cell line-derived neurotrophic factor (GDNF), improved survival of neurones exposed to NO donors. In addition p38 MAP kinase was activated by NO exposure and inhibition of p38 signalling led to neuronal and axonal survival effects. OCM and IGF-1 (but not GDNF) reduced p38 activation in NO-exposed cortical neurones. OCM, IGF-1 and GDNF improved axon survival in cultures exposed to NO, a process dependent on mitogen-activated protein kinase/extracellular signal-related kinase signalling. This study emphasizes that different mechanisms may underlie neuronal/axonal destructive processes, and suggests that trophic factors may modulate NO-mediated neurone/axon destruction via specific pathways. [source]

    AMP-activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over-nourished sheep

    THE JOURNAL OF PHYSIOLOGY, Issue 10 2008
    Mei J. Zhu
    Maternal obesity and over-nutrition give rise to both obstetric problems and neonatal morbidity. The objective of this study was to evaluate effects of maternal obesity and over-nutrition on signalling of the AMP-activated protein kinase (AMPK) pathway in fetal skeletal muscle in an obese pregnant sheep model. Non-pregnant ewes were assigned to a control group (Con, fed 100% of NRC nutrient recommendations, n= 7) or obesogenic group (OB, fed 150% of National Research Council (NRC) recommendations, n= 7) diet from 60 days before to 75 days after conception (term 150 days) when fetal semitendinosus skeletal muscle (St) was sampled. OB mothers developed severe obesity accompanied by higher maternal and fetal plasma glucose and insulin levels. In fetal St, activity of phosphoinositide-3 kinase (PI3K) associated with insulin receptor substrate-1 (IRS-1) was attenuated (P < 0.05), in agreement with the increased phophorylation of IRS-1 at serine 1011. Phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172, acetyl-CoA carboxylase at Ser 79, tuberous sclerosis 2 at Thr 1462 and eukaryotic translation initiation factor 4E-binding protein 1 at Thr 37/46 were reduced in OB compared to Con fetal St. No difference in energy status (AMP/ATP ratio) was observed. The expression of protein phosphatase 2C was increased in OB compared to Con fetal St. Plasma tumour necrosis factor , (TNF,) was increased in OB fetuses indicating an increased inflammatory state. Expression of peroxisome proliferator-activated receptor , (PPAR,) was higher in OB St, indicating enhanced adipogenesis. The glutathione: glutathione disulphide ratio was also lower, showing increased oxidative stress in OB fetal St. In summary, we have demonstrated decreased signalling of the AMPK system in skeletal muscle of fetuses of OB mothers, which may play a role in altered muscle development and development of insulin resistance in the offspring. [source]

    Isothiocyanate E-4IB induces MAPK activation, delayed cell cycle transition and apoptosis

    CELL PROLIFERATION, Issue 3 2007
    J. Bodo
    Methods and results: In the current investigation, we examined the consequence of activating of signalling pathways during the release the cells from the block at G1/S boundary by synthetic isothiocyanate E-4IB. Using synchronized leukaemic HL60 cells, we show that activation of mitogen-activated protein kinases ERK1/2, c-Jun N-terminal kinase and p38 signalling pathways by E-4IB are coupled with delayed transition through the cell cycle and rapid cell cycle arrest resulted in diminished mitochondrial membrane potential culminating in apoptosis. These events were accompanied by histone deacetylase inhibition, increase of double strand DNA breaks detected by histone H2AX phosphorylation and up-regulation of cell cycle regulatory protein p21 and phosphorylation of CDC25C phosphatase. Conclusion: These findings suggest that the activation of mitogen-activated protein kinases signalling pathways, followed by the induction cell cycle arrest and apoptosis, might be responsible for anticancer activities of E-4IB. [source]