Alpha(v)beta3 integrin expression up-regulates cdc2, which modulates cell migration.
Alpha(v)beta3 integrin expression up-regulates cdc2, which modulates cell migration.
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DOI：
10.1083/jcb.200212172
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发表时间：
2003-05-26
期刊：
影响因子：
--
通讯作者：
Languino LR
中科院分区：
文献类型：
--
作者：
Manes T;Zheng DQ;Tognin S;Woodard AS;Marchisio PC;Languino LR
已显示αvβ3整联蛋白通过激活细胞内信号传导途径促进细胞迁移。我们在这里描述了一种调节细胞迁移的新途径，该途径由αvβ3激活，并作为下游效应物由cdc 2（cdk 1）激活。我们报告了LNCaP（β3-LNCaP）前列腺癌细胞中αvβ3的表达导致cdc 2 mRNA水平增加（通过基因表达分析评估），以及cdc 2蛋白和激酶活性水平增加。我们提供了三条证据，证明cdc 2水平的增加有助于不同细胞类型中整合素配体的能动表型。首先，cdc 2水平的增加与癌细胞的运动表型相关。第二，cdc 2的异位表达增加细胞迁移，而显性阴性cdc 2的表达抑制迁移。第三，cdc 2抑制剂减少细胞迁移而不影响细胞粘附。我们还表明，cdc 2通过与细胞周期蛋白B2的特异性关联增加细胞迁移，我们解开了一个新的细胞运动途径，涉及cdc 2的下游，钙调蛋白。此处显示CDC 2和钙调蛋白定位于运动细胞的膜皱褶中。这些结果表明cdc 2是αvβ3整联蛋白的下游效应物，并且它促进细胞迁移。
The αvβ3 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 αvβ3 and, as downstream effector, by cdc2 (cdk1). We report that αvβ3 expression in LNCaP (β3-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 αvβ3 integrin, and that it promotes cell migration.
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影响因子：
11.4
作者：
BAILLY, E;DOREE, M;BORNENS, M
通讯作者：
BORNENS, M
DOI：
10.1083/jcb.130.2.441
发表时间：
1995-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Filardo EJ;Brooks PC;Deming SL;Damsky C;Cheresh DA
通讯作者：
Cheresh DA
影响因子：
56.9
作者：
Fang, F;Orend, G;Ruoslahti, E
通讯作者：
Ruoslahti, E
影响因子：
64.8
作者：
Clark, EA;Golub, TR;Hynes, RO
通讯作者：
Hynes, RO
DOI：
10.1083/jcb.149.5.1073
发表时间：
2000-05-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hirota T;Morisaki T;Nishiyama Y;Marumoto T;Tada K;Hara T;Masuko N;Inagaki M;Hatakeyama K;Saya H
通讯作者：
Saya H