NOK与Akt相互作用并增强Akt的活化(英文)

NOK Interacts With Akt and Enhances Its Activation

NOK是一个新近鉴定的受体型蛋白酪氨酸激酶分子,它能够促进肿瘤的形成和转移.前期的研究表明,NOK在小鼠前B细胞(BaF3)中能够激活磷脂酰肌醇3-激酶(PI3K)信号通路.但是,人们并不清楚NOK在细胞内是如何激活PI3K信号通路的.研究发现,NOK与PI3K下游的效应分子蛋白激酶B(Akt)具有直接的相互作用.并且,在人胚肾细胞(HEK293T)中,NOK能明显增强Akt的活性.通过NOK缺失突变体的免疫共沉淀实验,确定了Akt能直接结合NOK的激酶结构域.同时,Akt的激酶活性缺失体并不影响其与NOK的结合,但也观察到,持续活化的Akt跟NOK具有更强的相互作用.最后,发现NOK对胰岛素介导的Akt激活并没有产生叠加效应.实验结果显示,NOK可以与Akt直接相互作用并增强PI3K/Akt信号通路的活化.

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.