TY - JOUR
T1 - Activation of signal transduction pathways involving trkA, PLCγ-1, PKC isoforms and ERK-1/2 by tetanus toxin
AU - Gil, Carles
AU - Chaı̈b-Oukadour, Imane
AU - Pelliccioni, Patricia
AU - Aguilera, José
PY - 2000/9/15
Y1 - 2000/9/15
N2 - 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 Cγ-1 (PLCγ-1), and extracellular regulated kinases 1 and 2 (ERK-1/2) by TeTx in a synaptosome-enriched P2 fraction from rat brain is reported. TeTx induces clear translocation from the soluble (cytosolic) compartment to the particulate (membranous) compartment of PKC-β, -γ and -δ isoforms, whereas PKC-ε showed a slight decrease of its soluble fraction immunoreactivity. On the contrary, the PKC-ζ isoform shows no consistent response, whereas down-regulation of total PKC-α immunoreactivity is shown. Immunoprecipitation assays against phosphotyrosine show an increase of trkA and PLCγ-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. (C) 2000 Federation of European Biochemical Societies.
AB - 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 Cγ-1 (PLCγ-1), and extracellular regulated kinases 1 and 2 (ERK-1/2) by TeTx in a synaptosome-enriched P2 fraction from rat brain is reported. TeTx induces clear translocation from the soluble (cytosolic) compartment to the particulate (membranous) compartment of PKC-β, -γ and -δ isoforms, whereas PKC-ε showed a slight decrease of its soluble fraction immunoreactivity. On the contrary, the PKC-ζ isoform shows no consistent response, whereas down-regulation of total PKC-α immunoreactivity is shown. Immunoprecipitation assays against phosphotyrosine show an increase of trkA and PLCγ-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. (C) 2000 Federation of European Biochemical Societies.
KW - Clostridial neurotoxin
KW - Rat brain
KW - Signal transduction
KW - Synaptosome
U2 - 10.1016/S0014-5793(00)02002-0
DO - 10.1016/S0014-5793(00)02002-0
M3 - Article
SN - 0014-5793
VL - 481
SP - 177
EP - 182
JO - FEBS Letters
JF - FEBS Letters
ER -