Activation of signal transduction pathways involving trkA, PLCgamma-1, PKC isoforms and ERK-1/2 by tetanus toxin.
Previous reports have demonstrated that tetanus toxin (TeTx) induces activation and down-regulation of protein kinase C (PKC). In the present work the differential activation of PKC isoforms and of signal transduction pathways, including nerve growth factor receptor trkA, phospholipase Cgamma-1 (PLCgamma-1), and extracellular regulated kinases 1 and 2 (ERK-1/2) by TeTx in a synaptosome-enriched P(2) fraction from rat brain is reported. TeTx induces clear translocation from the soluble (cytosolic) compartment to the particulate (membranous) compartment of PKC-beta, -gamma and -delta isoforms, whereas PKC-epsilon showed a slight decrease of its soluble fraction immunoreactivity. On the contrary, the PKC-zeta isoform shows no consistent response, whereas down-regulation of total PKC-alpha immunoreactivity is shown. Immunoprecipitation assays against phosphotyrosine show an increase of trkA and PLCgamma-1 phosphorylation. Moreover, trkA activation is corroborated using phospho-specific antibodies against phosphorylated trkA. On the other hand, TeTx-induced stimulation of mitogen-activated protein (MAP) kinase activity is observed, this event also being detected by Western analysis using phospho-specific antibodies against ERK-1/2.
Gil
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Departament de Bioquímica i de Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 (Barcelona), Catalunya, Bellaterra, Spain.
Chaïb-Oukadour
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Pelliccioni
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P
Aguilera
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J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000201:enzymology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012995:Solubility / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013744:Tetanus Toxin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D013744:Tetanus Toxin; D019000:Phosphotyrosine; D020917:Receptor, trkA; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D013755:Tetradecanoylphorbol Acetate