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Regulation of JNK signalling pathway by GM1
Author(s) -
Mo L.,
Neff N. H.,
Hadjiconstantinou M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.38_5.x
Subject(s) - trk receptor , phosphorylation , neurotrophin , microbiology and biotechnology , mapk/erk pathway , kinase , tropomyosin receptor kinase a , signal transduction , biology , hippocampal formation , tropomyosin receptor kinase b , mitogen activated protein kinase , neurotrophic factors , receptor , chemistry , neuroscience , biochemistry
The ganglioside GM1 exerts pleitropic trophic actions in both the central and peripheral nervous systems in vivo and in vitro . Our previous research has shown that in brain tissue, GM1 is capable of inducing tyrosine phosphorylation of Trk receptors for the neurotrophins and initiating signaling via the MEK/ERK pathway. In order to better understand the intracellular signalling events associated with GM1, we investigated the effects of GM1 on the JNK pathway and its downstream transcriptional factor targets. Incubating slices from hippocampus of young or aged rats with GM1 increased the content of phosphorylated (p) JNK and augmented JNK kinase activity. The GM1‐induced phosphorylation/activation of JNK was accompanied by an increase in phosphorylated (p) c‐Jun and (p) Elk1, but not (p) ATF, transcription factors. Furthermore, addition of GM1 to hippocampal slices induced enhanced AP‐1 DNA binding activity. A similar response was observed when slices were treated with the neurotrophins NGF and BDNF. Both the GM1‐ and neurotrophin‐induced activation of the JNK pathway were blocked by the selective Trk kinase inhibitor AG879. Taken together, these data suggest that the molecular mechanisms of GM1 actions may include recruitment of the JNK pathway. Acknowledgements: Supported, in part, by grant AG10530.