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GM1 ganglioside induces phosphorylation and activation of Trk and Erk in brain
Author(s) -
Duchemin AnneMarie,
Ren Qun,
Mo Lili,
Neff Norton H.,
Hadjiconstantinou Maria
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.1471-4159.2002.00831.x
Subject(s) - trk receptor , tropomyosin receptor kinase a , tropomyosin receptor kinase b , autophosphorylation , phosphorylation , mapk/erk pathway , microbiology and biotechnology , tropomyosin receptor kinase c , protein kinase b , biology , tyrosine kinase , kinase , neurotrophin , protein kinase a , chemistry , signal transduction , biochemistry , receptor , neurotrophic factors , platelet derived growth factor receptor , growth factor
Abstract We investigated the ability of GM1 to induce phosphorylation of the tyrosine kinase receptor for neurotrophins, Trk, in rat brain, and activation of possible down‐stream signaling cascades. GM1 increased phosphorylated Trk (pTrk) in slices of striatum, hippocampus and frontal cortex in a concentration‐ and time‐dependent manner, and enhanced the activity of Trk kinase resulting in receptor autophosphorylation. The ability of GM1 to induce pTrk was shared by other gangliosides, and was blocked by the selective Trk kinase inhibitors K252a and AG879. GM1 induced phosphorylation of TrkA > TrkC > TrkB in a region‐specific distribution. Adding GM1 to brain slices activated extracellular‐regulated protein kinases (Erks) in all three brain regions studied. In striatum, GM1 elicited activation of Erk2 > Erk1 in a time‐and concentration‐dependent manner. The GM1 effect on Erk2 was mimicked by other gangliosides, and was blocked by the Trk kinase inhibitors K252a and AG879. Pertussis toxin, as well as Src protein tyrosine kinase and protein kinase C inhibitors, did not prevent the GM1‐induced activation of Erk2, apparently excluding the participation of Gi and Gq/11 protein‐coupled receptors. Intracerebroventricular administration of GM1 induced a transient phosphorylation of TrkA and Erk1/2 in the striatum and hippocampus complementing the in situ studies. These observations support a role for GM1 in modulating Trk and Erk phosphorylation and activity in brain.