Role of palladin phosphorylation by extracellular signal-regulated kinase in cell migration.
Role of palladin phosphorylation by extracellular signal-regulated kinase in cell migration.
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细胞外信号调节激酶在细胞迁移中通过细胞外信号调节激酶的磷酸化作用。
DOI：
10.1371/journal.pone.0029338
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Senga T
中科院分区：
文献类型：
--
作者：
Asano E;Maeda M;Hasegawa H;Ito S;Hyodo T;Yuan H;Takahashi M;Hamaguchi M;Senga T
肌动蛋白结合蛋白的磷酸化在肌动蛋白细胞骨架重塑中起着关键作用，从而调节细胞迁移。Palladin是一种被生长因子刺激磷酸化的肌动蛋白结合蛋白；然而，涉及的蛋白激酶的身份仍然难以捉摸。在这项研究中，我们报道了Palladin是一种新的细胞外信号调节激酶(ERK)底物。化学抑制剂抑制ERK的激活降低了Palladin的磷酸化，而仅表达活性的MEK就足以使其磷酸化。此外，体外激酶实验证明ERK可以直接使Palladin磷酸化。我们发现Ser77和Ser197是磷酸化所必需的残基。虽然这些残基的磷酸化不是肌动蛋白细胞骨架组织所必需的，但我们发现非磷酸化的Palladin的表达促进了细胞的迁移。最后，我们发现磷酸化抑制了Palladin与Abl酪氨酸激酶的结合。综上所述，我们的结果表明ERK对Palladin的磷酸化具有抗迁移功能，可能是通过调节与调节细胞迁移的分子的相互作用来实现的。
Phosphorylation of actin-binding proteins plays a pivotal role in the remodeling of the actin cytoskeleton to regulate cell migration. Palladin is an actin-binding protein that is phosphorylated by growth factor stimulation; however, the identity of the involved protein kinases remains elusive. In this study, we report that palladin is a novel substrate of extracellular signal-regulated kinase (ERK). Suppression of ERK activation by a chemical inhibitor reduced palladin phosphorylation, and expression of active MEK alone was sufficient for phosphorylation. In addition, an in vitro kinase assay demonstrated direct palladin phosphorylation by ERK. We found that Ser77 and Ser197 are essential residues for phosphorylation. Although the phosphorylation of these residues was not required for actin cytoskeletal organization, we found that expression of non-phosphorylated palladin enhanced cell migration. Finally, we show that phosphorylation inhibits the palladin association with Abl tyrosine kinase. Taken together, our results indicate that palladin phosphorylation by ERK has an anti-migratory function, possibly by modulating interactions with molecules that regulate cell migration.
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影响因子：
8
作者：
Goicoechea, S. M.;Bednarski, B.;Garcia-Mata, R.;Prentice-Dunn, H.;Kim, H. J.;Otey, C. A.
通讯作者：
Otey, C. A.
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
DOI：
10.1083/jcb.146.1.149
发表时间：
1999-07-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nguyen DH;Catling AD;Webb DJ;Sankovic M;Walker LA;Somlyo AV;Weber MJ;Gonias SL
通讯作者：
Gonias SL
影响因子：
4.8
作者：
Liu, ZX;Yu, CF;Cantley, LG
通讯作者：
Cantley, LG
影响因子：
3.7
作者：
Kurata, H;Thant, AA;Hamaguchi, M
通讯作者：
Hamaguchi, M