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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism*
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Animals
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Aurora Kinase A
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Aurora Kinases
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Cell Line, Tumor
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GTPase-Activating Proteins / genetics
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GTPase-Activating Proteins / metabolism*
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Humans
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Mice
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Mice, SCID
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Mutation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Xenograft Model Antitumor Assays
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ral GTP-Binding Proteins / genetics
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ral GTP-Binding Proteins / metabolism*
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ras Proteins / metabolism*
Substances
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ATP-Binding Cassette Transporters
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GTPase-Activating Proteins
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RALBP1 protein, human
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Aurka protein, mouse
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Aurora Kinase A
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Aurora Kinases
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Protein Serine-Threonine Kinases
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RALA protein, human
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ral GTP-Binding Proteins
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ras Proteins