Aurora kinase A interacts with H-Ras and potentiates Ras-MAPK signaling

被引:23
作者
Umstead, MaKendra [1 ,2 ,3 ]
Xiong, Jinglin [2 ,3 ,4 ]
Qi, Qi [2 ,3 ]
Du, Yuhong [2 ,3 ]
Fu, Haian [2 ,3 ,5 ]
机构
[1] Emory Univ, Grad Program Canc Biol, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Emory Chem Biol Discovery Ctr, Atlanta, GA 30322 USA
[4] Cent S Univ, Xiangya Hosp, Dept Dermatol, Changsha, Hunan, Peoples R China
[5] Winship Canc Inst, Atlanta, GA 30322 USA
关键词
Aurora A; Ras; Raf; MAPK; protein-protein interactions;
D O I
10.18632/oncotarget.15049
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In cancer, upregulated Ras promotes cellular transformation and proliferation in part through activation of oncogenic Ras-MAPK signaling. While directly inhibiting Ras has proven challenging, new insights into Ras regulation through protein-protein interactions may offer unique opportunities for therapeutic intervention. Here we report the identification and validation of Aurora kinase A (Aurora A) as a novel Ras binding protein. We demonstrate that the kinase domain of Aurora A mediates the interaction with the N-terminal domain of H-Ras. Further more, the interaction of Aurora A and H-Ras exists in a protein complex with Raf-1. We show that binding of H-Ras to Raf-1 and subsequent MAPK signaling is enhanced by Aurora A, and requires active H-Ras. Thus, the functional linkage between Aurora A and the H-Ras/Raf-1 protein complex may provide a mechanism for Aurora A's oncogenic activity through direct activation of the Ras/MAPK pathway.
引用
收藏
页码:28359 / 28372
页数:14
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