Brevetoxin-induced phosphorylation of Pyk2 and Src in murine neocortical neurons involves distinct signaling pathways

Zhengyu Cao, Joju George, Daniel G. Baden, Thomas F. Murray

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Brevetoxins (PbTx-1 to PbTx-10) are potent lipid soluble polyether neurotoxins produced by the marine dinoflagellate Karenia brevis. Brevetoxins bind to site 5 of the α-subunit of voltage-gated sodium channels (VGSCs) and augment Na+ influx. In neocortical neurons brevetoxins elevate intracellular Ca2+ and augment NMDA receptor signaling. In this study, we explored the effects of PbTx-2 on Pyk2 and Src activation in neocortical neurons. We found that both Pyk2 and Src were activated following PbTx-2 exposure. PbTx-2-induced Pyk2 Tyr402 phosphorylation was dependent on elevation of Ca2+ influx through NMDA receptors. Moreover, Pyk2 Tyr402 phosphorylation was also found to require PKC activation inasmuch as RO-31-8425 and GF 109203x both attenuated the response. In contrast, PbTx-2-induced Src Tyr416 phosphorylation involved a Gq-coupled receptor inasmuch as U73122, a specific PLC inhibitor, abolished the response. This Gq-coupled receptor appears to be mGluR 5. The PKCδ inhibitor rottlerin abolished PbTx-2-induced Src activation demonstrating that this isoform of PKC is involved in the activation of Src by PbTx-2. Considered together these data suggest that although activation of neuronal Pyk2 and Src result from PbTx-2 stimulation of VGSC, engagement of these two non-receptor tyrosine kinases involves distinct signaling pathways.

Original languageEnglish
Pages (from-to)17-27
Number of pages11
JournalBrain Research
Volume1184
Issue number1
DOIs
StatePublished - Dec 12 2007

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Phosphorylation
Neurons
Voltage-Gated Sodium Channels
N-Methyl-D-Aspartate Receptors
Dinoflagellida
Neurotoxins
Ptychodiscus brevis T2 toxin
brevetoxin
Protein-Tyrosine Kinases
Protein Isoforms
Lipids

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Brevetoxin-induced phosphorylation of Pyk2 and Src in murine neocortical neurons involves distinct signaling pathways. / Cao, Zhengyu; George, Joju; Baden, Daniel G.; Murray, Thomas F.

In: Brain Research, Vol. 1184, No. 1, 12.12.2007, p. 17-27.

Research output: Contribution to journalArticle

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