Aurora kinase A interacts with H-Ras and potentiates Ras-MAPK signaling
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MaKendra Umstead1,2, Jinglin Xiong2,3, Qi Qi2, Yuhong Du2, Haian Fu2,4
1Graduate Program in Cancer Biology, Emory University, Atlanta, GA, USA
2Department of Pharmacology and Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA, USA
3Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
4Winship Cancer Institute, Atlanta, GA, USA
Haian Fu, email: email@example.com
Keywords: Aurora A, Ras, Raf, MAPK, protein-protein interactions
Received: September 14, 2016 Accepted: January 07, 2017 Published: February 03, 2017
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.
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