Aurora-A Phosphorylates, Activates, and Relocalizes the Small GTPase RalA

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 11/2009; 30(2):508-23. DOI: 10.1128/MCB.00916-08
Source: PubMed

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.

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Available from: David Kashatus, Sep 26, 2015
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    • "Our knowledge of the roles of RLIP76 and RalA in mitosis has been extended more recently, as both proteins have been implicated in mitochondrial fission (Kashatus et al., 2011): RalA phosphorylation by AuroraA leads to RalA and RLIP76 localization to mitochondria and, once there, they regulate the phosphorylation of the Drp1 GTPase by Cdk1-CyclinB. RLIP76 is usually located in the cytoplasm, but translocates to the membrane upon activation by Ral proteins (Lim et al., 2010). It contains two putative ATP binding sites (residues 65–80 and 415–448) (Awasthi et al., 2001), which allow membrane-associated RLIP76 to function as an ATP-dependent transporter protein that acts as an efflux pump for small molecules including anticancer drugs and endogenous metabolites (Vatsyayan et al., 2010). "
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