標題: Identification of V23RalA-Ser(194) as a critical mediator for aurora-A-induced cellular motility and transformation by small pool expression screening
作者: Wu, JC
Chen, TY
Yu, CTR
Tsai, SJ
Hsu, JM
Tang, MJ
Chou, CK
Lin, WJ
Yuan, CJ
Huang, CYF
生物科技學系
Department of Biological Science and Technology
公開日期: 11-Mar-2005
摘要: 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-Ser(194) was the phosphorylation site for Aurora-A. Ectopic expression of V23RalA-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 V23RalA-S194A in MDCK Aurora-Astable 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 Ser(194) to promote collagen I-induced cell motility and anchorage-independent growth in MDCK epithelial cells.
URI: http://dx.doi.org/10.1074/jbc.M411068200
http://hdl.handle.net/11536/13906
ISSN: 0021-9258
DOI: 10.1074/jbc.M411068200
期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
Volume: 280
Issue: 10
起始頁: 9013
結束頁: 9022
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