title: Epidermal growth factor receptor is involved in clusterin-induced astrocyte proliferation.
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.
authors.affiliation: Department of Pharmacology, BK21 Program for Medical Sciences, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Shim
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Shin
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Byeong-Moo
authors.initials: BM
authors.lastname: Kim
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Park
authors.forename: Bon-Hong
authors.initials: BH
authors.lastname: Min
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D051152:Clusterin / Q000494:pharmacology* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019908:Proto-Oncogene Proteins c-raf / Q000187:drug effects; D011799:Quinazolines; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D051152:Clusterin; D008934:Mitogens; D011799:Quinazolines; D034741:RNA, Small Interfering; D020032:Tyrphostins; C101044:RTKI cpd; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases