Identification of V23RalA-Ser194 as a critical mediator for Aurora-A-induced cellular motility and transformation by small pool expression screening

Jiunn Chyi Wu, Tzong Yueh Chen, Chang Tze R. Yu, Si Jie Tsai, Jung Mao Hsu, Ming Jer Tang, Chen Kung Chou, Wey Jinq Lin, Chiun-Jye Yuan, Chi Ying F. Huang*

*Corresponding author for this work

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Human Aurora kinases have three gene family members: Aurora-A, Aurora-B, and Aurora-C. It is not yet established what the specificity of these kinases are and what signals relayed by their reactions. Therefore, we employed small pool expression screening to search for downstream substrates of Aurora-A. Interestingly, all of the identified Aurora-A substrates were resistant to serve as substrates for Aurora-B or Aurora-C, suggesting that these Aurora family members may have distinct substrate specificity for propagation of diverse signaling pathways, even though they share a conserved catalytic kinase domain. Of the candidate substrates, Aurora-A could increase the functional activity of RalA. Mutational analysis revealed that RalA-Ser194 was the phosphorylation site for Aurora-A. Ectopic expression of V23Ra1A-WT could enhance collagen I-induced cell migration and anchorage-independent growth in Madin-Darby canine kidney (MDCK) Aurora-A stable cell lines. In contrast, overexpression of 23RalA-S194A in MDCK Aurora-A-stable cell lines abolished the intrinsic migration and transformation abilities of Aurora-A. To our knowledge, this is the first systematic search for the downstream substrates of Aurora-A kinase. Moreover, these results support the notion that Aurora-A may act in concert with V23RalA through protein phosphorylation on Ser194 to promote collagen I-induced cell motility and anchorage-independent growth in MDCK epithelial cells.

Original languageEnglish
Pages (from-to)9013-9022
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number10
DOIs
StatePublished - 11 Mar 2005

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