Kank regulates RhoA-dependent formation of actin stress fibers and cell migration via 14-3-3 in PI3K-Akt signaling.
Kank regulates RhoA-dependent formation of actin stress fibers and cell migration via 14-3-3 in PI3K-Akt signaling.
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DOI：
10.1083/jcb.200707022
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发表时间：
2008-05-05
期刊：
影响因子：
--
通讯作者：
Kiyama R
中科院分区：
文献类型：
--
作者：
Kakinuma N;Roy BC;Zhu Y;Wang Y;Kiyama R
PI3K /Akt信号被胰岛素、表皮生长因子等生长因子激活，调控细胞周期、细胞凋亡、细胞生长和细胞迁移等多种功能。在这里，我们发现Kank是位于PI3K下游的Akt底物，是一个14-3-3结合蛋白。Kank与14-3-3的相互作用受胰岛素和EGF调控，并通过Akt磷酸化Kank介导。在表达Kank的NIH3T3细胞中，肌动蛋白应激纤维的数量减少，14-3-3的共表达破坏了这种作用。Kank还通过14-3-3结合抑制胰岛素诱导的细胞迁移。此外，Kank通过结合14-3-3抑制胰岛素和活跃的akt依赖性RhoA活化。基于这些发现，我们假设Kank通过抑制RhoA活性负向调节肌动蛋白应激纤维的形成和细胞迁移，RhoA活性是由Kank与PI3K-Akt信号传导中的14-3-3结合控制的。
Phosphoinositide-3 kinase (PI3K)/Akt signaling is activated by growth factors such as insulin and epidermal growth factor (EGF) and regulates several functions such as cell cycling, apoptosis, cell growth, and cell migration. Here, we find that Kank is an Akt substrate located downstream of PI3K and a 14-3-3–binding protein. The interaction between Kank and 14-3-3 is regulated by insulin and EGF and is mediated through phosphorylation of Kank by Akt. In NIH3T3 cells expressing Kank, the amount of actin stress fibers is reduced, and the coexpression of 14-3-3 disrupted this effect. Kank also inhibits insulin-induced cell migration via 14-3-3 binding. Furthermore, Kank inhibits insulin and active Akt-dependent activation of RhoA through binding to 14-3-3. Based on these findings, we hypothesize that Kank negatively regulates the formation of actin stress fibers and cell migration through the inhibition of RhoA activity, which is controlled by binding of Kank to 14-3-3 in PI3K–Akt signaling.
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影响因子：
3.3
作者：
Kurokawa, K;Matsuda, M
通讯作者：
Matsuda, M
影响因子：
9.2
作者：
Gohla, A;Bokoch, GM
通讯作者：
Bokoch, GM
影响因子：
4.8
作者：
Aoki, M;Schetter, C;Vogt, PK
通讯作者：
Vogt, PK
影响因子：
--
作者：
Hsu, SY;Kaipia, A;Hsueh, AJW
通讯作者：
Hsueh, AJW
DOI：
10.1073/pnas.92.22.10142
发表时间：
1995-10-24
影响因子：
11.1
作者：
BONNEFOYBERARD, N;LIU, YC;ALTMAN, A
通讯作者：
ALTMAN, A