Neuroreport · 2009 · 19 citations · 21 references
Life SciencesCell BiologyNeuroscienceCell ProliferationCell SignalingSignal TransductionAstrocyte BiologyCell Signaling NetworksGlial Cell SignalingGrowth Factor SignalingMitogenic SignalingRas Family OncogenesEpidermal Growth Factor Receptor SignalingErk SignalingExtracellular Signal-regulated Kinase PathwayExtracellular Signal-regulated Kinase SignalingMitogenic Signal TransductionMitogenic Signaling PathwaysProtein Tyrosine PhosphorylationRaf-mek-erk Signaling
We previously reported that clusterin enhances astrocyte proliferation and extracellular signal-regulated kinase (ERK) activity. It, however, remains largely unknown how clusterin promotes cell growth. Here, we investigate the signaling pathway and related molecules underlying astrocyte proliferation by clusterin. Exogenous clusterin stimulates Ras-dependent Raf-1/mitogen-activated protein kinase kinase (MEK)/ERK activation. Clusterin-induced astrocyte proliferation and ERK1/2 phosphorylation were abrogated by either AG1478 (an inhibitor of epidermal growth factor receptor, EGFR) or EGFR small interfering RNA. Furthermore, clusterin treatment provoked tyrosine phosphorylation of EGFR (pY(1173)), which was also blocked by AG1478. These results suggest that clusterin requires EGFR activation to deliver its mitogenic signal through the Ras/Raf-1/MEK/ERK signaling cascade in astrocytes.
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