mda-9/Syntenin Protein Positively Regulates the Activation of Akt Protein by Facilitating Integrin-linked Kinase Adaptor Function during Adhesion to Type I Collagen
mda-9/Syntenin Protein Positively Regulates the Activation of Akt Protein by Facilitating Integrin-linked Kinase Adaptor Function during Adhesion to Type I Collagen
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DOI：
10.1074/jbc.m110.206789
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发表时间：
2011-09-23
影响因子：
4.8
通讯作者：
Lee, Jeong-Hyung
中科院分区：
文献类型：
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作者：
Hwangbo, Cheol;Park, Juhee;Lee, Jeong-Hyung
整合素连接激酶（ILK）-PINCH 1-α-小蛋白（IPP）复合物作为调节各种细胞过程的整合素的信号传导平台发挥作用。ILK作为IPP复合物组装的中心适配器发挥作用。我们在这里报告，mda-9/syntenin，癌症转移的正调节因子，调节Akt（也称为蛋白激酶B）的激活，通过促进ILK适配器的功能，在粘附到I型胶原蛋白（COL-I）在人乳腺癌细胞。COL-I刺激诱导Akt磷酸化和质膜转位。抑制mda-9/syntenin或突变体ILK（E359 K）的表达显著阻断了ILK和Akt向质膜的转运。mda-9/syntenin与ILK相关，并且通过COL-I刺激在质膜处增加这种关联。mda-9/syntenin的敲低损害了COL-I诱导的ILK与Akt的结合以及ILK-Akt复合物的质膜靶向。这些结果表明，mda-9/syntenin调节Akt的激活，通过控制Akt的质膜靶向，通过一种机制，促进Akt与ILK在质膜上的协会在粘附到COL-I。值得注意的是，mda-9/syntenin的抑制损害了COL-I诱导的IPP复合物的质膜易位和整合素β 1-IPP信号复合物的组装。因此，我们的研究定义了mda-9/syntenin在ILK适配器功能中的作用，并描述了mda-9/syntenin调节细胞迁移的新机制。
The integrin-linked kinase (ILK)-PINCH1-alpha-parvin (IPP) complex functions as a signaling platform for integrins that modulates various cellular processes. ILK functions as a central adaptor for the assembly of IPP complex. We report here that mda-9/syntenin, a positive regulator of cancer metastasis, regulates the activation of Akt (also known as protein kinase B) by facilitating ILK adaptor function during adhesion to type I collagen (COL-I) in human breast cancer cells. COL-I stimulation induced the phosphorylation and plasma membrane translocation of Akt. Inhibition of mda-9/syntenin or expression of mutant ILK (E359K) significantly blocked the translocation of both ILK and Akt to the plasma membrane. mda-9/syntenin associated with ILK, and this association was increased at the plasma membrane by COL-I stimulation. Knockdown of mda-9/syntenin impaired COL-I-induced association of ILK with Akt and plasma membrane targeting of ILK-Akt complex. These results demonstrated that mda-9/syntenin regulates the activation of Akt by controlling the plasma membrane targeting of Akt via a mechanism that facilitates the association of Akt with ILK at the plasma membrane during adhesion to COL-I. On a striking note, inhibition of mda-9/syntenin impaired COL-I-induced plasma membrane translocation of the IPP complex and assembly of integrin beta 1-IPP signaling complexes. Thus, our study defines the role of mda-9/syntenin in ILK adaptor function and describes a new mechanism of mda-9/syntenin for regulation of cell migration.