Low substratum rigidity of collagen gel promotes ERK phosphorylation via lipid raft to augment cell migration

Wei Chun Wei, Yu Chih Hsu, Wen-Tai Chiu, Chau Zen Wang, Ching Ming Wu, Yang-Gao Wang, Meng-Ru Shen, Ming-Jer Tang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1111-1124
Number of pages14
JournalJournal of Cellular Biochemistry
Volume103
Issue number4
DOIs
Publication statusPublished - 2008 Mar 1

Fingerprint

Phosphorylation
Rigidity
Cell Movement
Collagen
Gels
Lipids
Degradation
Focal Adhesions
Cyclodextrins
Adhesion
Madin Darby Canine Kidney Cells
Mitogen-Activated Protein Kinase Kinases
Cultured Cells
Phosphotransferases
Down-Regulation
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Low substratum rigidity of collagen gel promotes ERK phosphorylation via lipid raft to augment cell migration",
abstract = "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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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.

In: Journal of Cellular Biochemistry, Vol. 103, No. 4, 01.03.2008, p. 1111-1124.

Research output: Contribution to journalArticle

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