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 language | English |
|---|---|
| Pages (from-to) | 435-439 |
| Number of pages | 5 |
| Journal | NeuroReport |
| Volume | 20 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2009 Mar 4 |
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Keywords
- Astrocytes
- Clusterin
- Epidermal growth factor receptor
- Extracellular signal-regulated kinase
- Tyrosine phosphorylation
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Epidermal growth factor receptor is involved in clusterin-induced astrocyte proliferation. / Shim, Young Jun; Shin, Yong Jae; Jeong, Seong Yun; Kang, Sang Wook; Kim, Byeong Moo; Park, In Sun; Min, Bon Hong.
In: NeuroReport, Vol. 20, No. 4, 04.03.2009, p. 435-439.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epidermal growth factor receptor is involved in clusterin-induced astrocyte proliferation
AU - Shim, Young Jun
AU - Shin, Yong Jae
AU - Jeong, Seong Yun
AU - Kang, Sang Wook
AU - Kim, Byeong Moo
AU - Park, In Sun
AU - Min, Bon Hong
PY - 2009/3/4
Y1 - 2009/3/4
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Clusterin
KW - Epidermal growth factor receptor
KW - Extracellular signal-regulated kinase
KW - Tyrosine phosphorylation
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U2 - 10.1097/WNR.0b013e3283262df8
DO - 10.1097/WNR.0b013e3283262df8
M3 - Article
VL - 20
SP - 435
EP - 439
JO - NeuroReport
JF - NeuroReport
SN - 0959-4965
IS - 4
ER -