Signal Transduction of Differentiation-Induction by Mannosylerythritol Lipid on PC 12 Pheochromocytoma Cells

Abstract

We reported here that a microbial extracellular glycolipid, mannosylerythritol lipid (MEL) induced the neuronal differentiation of PC 12 cells and stimulated the action of nerve growth factor (NGF). MEL committed the neurite outgrowth of PC 12 cells even in the presence of antibody against low-affinity NGF receptor (p75NGFR) which has been known as the competitive inhibitor of the signal transduction of NGF. This result implies that MEL and NGF could induce the differentiation of neurite outgrowth of PC 12 cells by different mechanisms. The results of Western blotting analysis demonstrated that addition of both NGF and MEL during the cultivation resulted the temporary disappearances of the expressions of p60src, focal adhesion protein tyrosine kinase (p125FAK) and high-affinity NGF receptor (p140trk). When MEL was tested for the regulated expression of these kinases, we found the similar downregulations of expressions of p60src and p125FAK, not of p140trk. Expression of epidermal growth factor receptor (p170EGFR) was unaffected by addition of MEL, irrespective of the presence or absence of NGF. Moreover, MEL also stimulated the phosphorylation of mitogen-activated protein (MAP) kinase. Taken together, these results suggest that MEL and NGF trigger different signal cascades for differentiation of PC 12 cells to commit the neurite outgrowth.KeywordsEpidermal Growth Factor ReceptorNerve Growth FactorNeurite OutgrowthNeuronal DifferentiationNerve Growth Factor ReceptorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.