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 (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.
journal_name
Neuroreportjournal_title
Neuroreportauthors
Shim YJ,Shin YJ,Jeong SY,Kang SW,Kim BM,Park IS,Min BHdoi
10.1097/WNR.0b013e3283262df8subject
Has Abstractpub_date
2009-03-04 00:00:00pages
435-9issue
4eissn
0959-4965issn
1473-558Xjournal_volume
20pub_type
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