Epidermal growth factor receptor is involved in clusterin-induced astrocyte proliferation

Young Jun Shim, Yong Jae Shin, Seong Yun Jeong, Sang Wook Kang, Byeong Moo Kim, In Sun Park, Bon Hong Min

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 (pY1173), 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.

Original languageEnglish
Pages (from-to)435-439
Number of pages5
JournalNeuroreport
Volume20
Issue number4
DOIs
Publication statusPublished - 2009 Mar 4

Keywords

  • Astrocytes
  • Clusterin
  • Epidermal growth factor receptor
  • Extracellular signal-regulated kinase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

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