Abstract
The small GTPase Ras, which transmits extracellular signals to the cell, and the kinase Aurora-A, which promotes proper mitosis, can both be inappropriately activated in human tumors. Here, we show that Aurora-A in conjunction with oncogenic Ras enhances transformed cell growth. Furthermore, such transformation and in some cases also tumorigenesis depend upon S194 of RalA, a known Aurora-A phosphorylation site. Aurora-A promotes not only RalA activation but also translocation from the plasma membrane and activation of the effector protein RalBP1. Taken together, these data suggest that Aurora-A may converge upon oncogenic Ras signaling through RalA.
Supplemental material for this article may be found at http://mcb.asm.org/.
We thank Mike White for plasmids pMT3-mycRalBP1 and pcDNA3-mycSec5.
This work is supported by NIH grants CA94184 and CA126903 (C.M.C.), CA42978 and CA67771 (C.J.D. and A.D.C.), and CA109550 (A.D.C.). C.M.C. is a Leukemia and Lymphoma Scholar, D.F.K. is a Leukemia and Lymphoma Fellow, and K.-H.L. and B.B.A. were Department of Defense Breast Cancer Research Predoctoral Scholars. D.C.B. is supported by an NIH T32 Training Fellowship.