NOK Interacts With Akt and Enhances Its Activation
NOK Interacts With Akt and Enhances Its Activation
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NOK 与 Akt 相互作用并增强其激活
DOI：
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发表时间：
2008
影响因子：
0.3
通讯作者：
Chang Zhi Jie
中科院分区：
文献类型：
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作者：
Liu Li;Li Ying-Hua;Chang Zhi Jie
NOK是一种新发现的能促进肿瘤发生和转移的受体蛋白酪氨酸激酶（PRTK）分子。以往的研究表明，NOK能激活稳定的BaF 3细胞中的磷脂酰肌醇3 '-激酶（PI 3 K）通路，但NOK在细胞中是如何激活PI 3 K的尚不清楚。在人胚肾293 T细胞中，NOK与PI 3 K下游效应子Akt相互作用，并增强其激活。缺失图谱显示蛋白激酶B（Akt）能够直接与NOK的激酶结构域接触，失活Akt激酶结构域显著降低了NOK与Akt之间的分子间相互作用，而组成型激活的Akt突变体与NOK之间的相互作用明显增强，NOK对胰岛素介导的Akt激活没有累加效应。结果表明，NOK可能与Akt复合，直接激活PI 3 K/Akt信号通路。
NOK is a newly identified receptor protein-tyrosine kinase(PRTK) molecule that can promote tumorigenesis and metastasis.Previous data showed that NOK could activate the phosphatidylinositol 3'-kinase(PI3K) pathway in stable BaF3 cells.But how does NOK activate PI3K in cells remains unknown.It was showed that NOK physically interacted with the PI3K downstream effector Akt and enhanced its activation in human embryo kidney 293T(HEK293T) cells.Deletion mapping indicated that protein kinase B(Akt) was able to directly contact with the kinase domain of NOK.Inactivating the Akt kinase domain significantly reduced the intermolecular interaction between NOK and Akt,while constitutively active mutant of Akt apparently had a stronger interaction with NOK.NOK did not have an additive effect on insulin-mediated Akt activation.Overall,the results indicate that NOK might complex with Akt and directly activate PI3K/Akt signaling pathway.