摘要
Previous study demonstrated that low substratum rigidity down-regulates focal adhesion proteins. In this study we found that cells cultured on collagen gel exhibited higher migration capacity than those cultured on collagen gel-coated dishes. Low rigidity of collagen gel induced delayed but persistent phosphorylation of ERK1/2. Inhibition of collagen gel-induced ERK1/2 phosphorylation by MEK inhibitors and ERK2 kinase mutant induced a rounding up of the cells and prevented collagen gel-induced cell migration. Interestingly, phosphorylated ERK1/2 induced by low rigidity was present in focal adhesion sites and the lipid raft. MβCD (Methyl-β-cyclodextrin), a lipid raft inhibitor, inhibited collagen gel-induced ERK1/2 phosphorylation, and cell migration. Overexpression of FAK C-terminal fragment (FRNK) in MDCK cells triggered ERK phosphorylation. Meanwhile, low substratum rigidity induced degradation of FAK into a 35 kDa C-terminal fragment. A calpain inhibitor that partially rescued FAK degradation also prevented low rigidity-induced ERK phosphorylation. However, MβCD did not prevent low rigidity-induced FAK degradation. Taken together, we demonstrate that the degradation product of FAK induced by collagen gel triggers activation of ERK1/2, which in turn facilitates cell spreading and migration through the lipid raft.
| 原文 | English |
|---|---|
| 頁（從 - 到） | 1111-1124 |
| 頁數 | 14 |
| 期刊 | Journal of Cellular Biochemistry |
| 卷 | 103 |
| 發行號 | 4 |
| DOIs | |
| 出版狀態 | Published - 2008 三月 1 |
指紋
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
引用此文
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Low substratum rigidity of collagen gel promotes ERK phosphorylation via lipid raft to augment cell migration. / Wei, Wei Chun; Hsu, Yu Chih; Chiu, Wen-Tai; Wang, Chau Zen; Wu, Ching Ming; Wang, Yang-Gao; Shen, Meng-Ru; Tang, Ming-Jer.
於: Journal of Cellular Biochemistry, 卷 103, 編號 4, 01.03.2008, p. 1111-1124.研究成果: Article
TY - JOUR
T1 - Low substratum rigidity of collagen gel promotes ERK phosphorylation via lipid raft to augment cell migration
AU - Wei, Wei Chun
AU - Hsu, Yu Chih
AU - Chiu, Wen-Tai
AU - Wang, Chau Zen
AU - Wu, Ching Ming
AU - Wang, Yang-Gao
AU - Shen, Meng-Ru
AU - Tang, Ming-Jer
PY - 2008/3/1
Y1 - 2008/3/1
N2 - Previous study demonstrated that low substratum rigidity down-regulates focal adhesion proteins. In this study we found that cells cultured on collagen gel exhibited higher migration capacity than those cultured on collagen gel-coated dishes. Low rigidity of collagen gel induced delayed but persistent phosphorylation of ERK1/2. Inhibition of collagen gel-induced ERK1/2 phosphorylation by MEK inhibitors and ERK2 kinase mutant induced a rounding up of the cells and prevented collagen gel-induced cell migration. Interestingly, phosphorylated ERK1/2 induced by low rigidity was present in focal adhesion sites and the lipid raft. MβCD (Methyl-β-cyclodextrin), a lipid raft inhibitor, inhibited collagen gel-induced ERK1/2 phosphorylation, and cell migration. Overexpression of FAK C-terminal fragment (FRNK) in MDCK cells triggered ERK phosphorylation. Meanwhile, low substratum rigidity induced degradation of FAK into a 35 kDa C-terminal fragment. A calpain inhibitor that partially rescued FAK degradation also prevented low rigidity-induced ERK phosphorylation. However, MβCD did not prevent low rigidity-induced FAK degradation. Taken together, we demonstrate that the degradation product of FAK induced by collagen gel triggers activation of ERK1/2, which in turn facilitates cell spreading and migration through the lipid raft.
AB - Previous study demonstrated that low substratum rigidity down-regulates focal adhesion proteins. In this study we found that cells cultured on collagen gel exhibited higher migration capacity than those cultured on collagen gel-coated dishes. Low rigidity of collagen gel induced delayed but persistent phosphorylation of ERK1/2. Inhibition of collagen gel-induced ERK1/2 phosphorylation by MEK inhibitors and ERK2 kinase mutant induced a rounding up of the cells and prevented collagen gel-induced cell migration. Interestingly, phosphorylated ERK1/2 induced by low rigidity was present in focal adhesion sites and the lipid raft. MβCD (Methyl-β-cyclodextrin), a lipid raft inhibitor, inhibited collagen gel-induced ERK1/2 phosphorylation, and cell migration. Overexpression of FAK C-terminal fragment (FRNK) in MDCK cells triggered ERK phosphorylation. Meanwhile, low substratum rigidity induced degradation of FAK into a 35 kDa C-terminal fragment. A calpain inhibitor that partially rescued FAK degradation also prevented low rigidity-induced ERK phosphorylation. However, MβCD did not prevent low rigidity-induced FAK degradation. Taken together, we demonstrate that the degradation product of FAK induced by collagen gel triggers activation of ERK1/2, which in turn facilitates cell spreading and migration through the lipid raft.
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U2 - 10.1002/jcb.21482
DO - 10.1002/jcb.21482
M3 - Article
C2 - 18027879
AN - SCOPUS:40349101964
VL - 103
SP - 1111
EP - 1124
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
IS - 4
ER -