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Alpha(v)beta3 integrin expression up-regulates cdc2, which modulates cell migration.
- Source :
-
The Journal of cell biology [J Cell Biol] 2003 May 26; Vol. 161 (4), pp. 817-26. - Publication Year :
- 2003
-
Abstract
- The alphavbeta3 integrin has been shown to promote cell migration through activation of intracellular signaling pathways. We describe here a novel pathway that modulates cell migration and that is activated by alphavbeta3 and, as downstream effector, by cdc2 (cdk1). We report that alphavbeta3 expression in LNCaP (beta3-LNCaP) prostate cancer cells causes increased cdc2 mRNA levels as evaluated by gene expression analysis, and increased cdc2 protein and kinase activity levels. We provide three lines of evidence that increased levels of cdc2 contribute to a motile phenotype on integrin ligands in different cell types. First, increased levels of cdc2 correlate with more motile phenotypes of cancer cells. Second, ectopic expression of cdc2 increases cell migration, whereas expression of dominant-negative cdc2 inhibits migration. Third, cdc2 inhibitors reduce cell migration without affecting cell adhesion. We also show that cdc2 increases cell migration via specific association with cyclin B2, and we unravel a novel pathway of cell motility that involves, downstream of cdc2, caldesmon. cdc2 and caldesmon are shown here to localize in membrane ruffles in motile cells. These results show that cdc2 is a downstream effector of the alphavbeta3 integrin, and that it promotes cell migration.
- Subjects :
- CDC2 Protein Kinase antagonists & inhibitors
CDC2 Protein Kinase genetics
Calmodulin-Binding Proteins metabolism
Cyclin B metabolism
Cyclin B2
Gene Expression Regulation, Enzymologic
HeLa Cells
Humans
RNA, Messenger genetics
RNA, Messenger metabolism
Tumor Cells, Cultured
Up-Regulation
CDC2 Protein Kinase metabolism
Cell Movement
Integrin alphaVbeta3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9525
- Volume :
- 161
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 12771130
- Full Text :
- https://doi.org/10.1083/jcb.200212172