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PMID: 19901077 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Aurora-A phosphorylates, activates, and relocalizes the small GTPase RalA.

Molecular and cellular biology ·Vol. 30 ·No. 2 ·2010-01-00 ·Pages 508-23

Lim KH, Brady DC, Kashatus DF, Ancrile BB, Der CJ, Cox AD, Counter CM

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.

MeSH Terms
ATP-Binding Cassette Transporters/genetics,metabolism Animals Aurora Kinase A Aurora Kinases Cell Line, Tumor GTPase-Activating Proteins/genetics,metabolism Humans Mice Mice, SCID Mutation Protein Serine-Threonine Kinases/genetics,metabolism Xenograft Model Antitumor Assays ral GTP-Binding Proteins/genetics,metabolism ras Proteins/metabolism
Chemicals
ATP-Binding Cassette Transporters GTPase-Activating Proteins RALBP1 protein, human Aurka protein, mouse Aurora Kinase A Aurora Kinases Protein Serine-Threonine Kinases RALA protein, human ral GTP-Binding Proteins ras Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lim Kian-Huat
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Brady Donita C
Kashatus David F
Ancrile Brooke B
Der Channing J
Cox Adrienne D
Counter Christopher M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.00916-08
Published
2010-01-00
Epub
2009-00-09
Pages
508-23
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2798468
Subset
IM
Grants
NCI NIH HHS · R01 CA042978 · United States
NCI NIH HHS · CA109550 · United States
NCI NIH HHS · R01 CA109550 · United States
NCI NIH HHS · R21 CA126903 · United States
NCI NIH HHS · CA94184 · United States
NCI NIH HHS · R01 CA094184 · United States
NCI NIH HHS · CA42978 · United States
NCI NIH HHS · CA126903 · United States
NCI NIH HHS · U19 CA067771 · United States
NCI NIH HHS · CA67771 · United States
External Links
PubMed source DOI: 10.1128/MCB.00916-08 PMC Full Text View journal details
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