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Ethanol inhibits L1 cell adhesion molecule activation of mitogen‐activated protein kinases
Author(s) -
Tang Ningfeng,
He Min,
O'Riordan Mary Ann,
Farkas Chloe,
Buck Kevin,
Lemmon Vance,
Bearer Cynthia F.
Publication year - 2006
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 - 10.1111/j.1471-4159.2006.03649.x
Subject(s) - fibroblast growth factor receptor 1 , microbiology and biotechnology , neurite , mapk/erk pathway , kinase , mitogen activated protein kinase , receptor tyrosine kinase , phosphorylation , chemistry , fibroblast growth factor , tyrosine kinase , signal transduction , tyrosine phosphorylation , biology , biochemistry , receptor , in vitro
Inhibition of the functions of L1 cell adhesion molecule (L1) by ethanol has been implicated in the pathogenesis of the neurodevelopmental aspects of the fetal alcohol syndrome (FAS). Ethanol at pharmacological concentrations has been shown to inhibit L1‐mediated neurite outgrowth of rat post‐natal day 6 cerebellar granule cells (CGN). Extracellular signal‐related kinases (ERK) 1/2 activation occurs following L1 clustering. Reduction in phosphoERK1/2 by inhibition of mitogen‐activated protein kinase kinase (MEK) reduces neurite outgrowth of cerebellar neurons. Here, we examine the effects of ethanol on L1 activation of ERK1/2, and whether this activation occurs via activation of fibroblast growth factor receptor 1 (FGFR1). Ethanol at 25 m m markedly inhibited ERK1/2 activation by both clustering L1 with cross‐linked monoclonal antibodies, or by L1‐Fc chimeric proteins. Clustering L1 with subsequent ERK1/2 activation did not result in tyrosine phosphorylation of the FGFR1. In addition, inhibition of FGFR1 tyrosine kinase blocked basic fibroblast growth factor (bFGF) activation of ERK1/2, but did not affect activation of ERK1/2 by clustered L1. We conclude that ethanol disrupts the signaling pathway between L1 clustering and ERK1/2 activation, and that this occurs independently of the FGFR1 pathway in cerebellar granule cells.