論文

査読有り 国際誌
2006年3月31日

Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes.

The Journal of biological chemistry
  • Aki Fujioka
  • ,
  • Kenta Terai
  • ,
  • Reina E Itoh
  • ,
  • Kazuhiro Aoki
  • ,
  • Takeshi Nakamura
  • ,
  • Shinya Kuroda
  • ,
  • Eisuke Nishida
  • ,
  • Michiyuki Matsuda

281
13
開始ページ
8917
終了ページ
26
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M509344200
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

To comprehend the Ras/ERK MAPK cascade, which comprises Ras, Raf, MEK, and ERK, several kinetic simulation models have been developed. However, a large number of parameters that are essential for the development of these models are still missing and need to be set arbitrarily. Here, we aimed at collecting these missing parameters using fluorescent probes. First, the levels of the signaling molecules were quantitated. Second, to monitor both the activation and nuclear translocation of ERK, we developed probes based on the principle of fluorescence resonance energy transfer. Third, the dissociation constants of Ras.Raf, Raf.MEK, and MEK.ERK complexes were estimated using a fluorescent tag that can be highlighted very rapidly. Finally, the same fluorescent tag was used to measure the nucleocytoplasmic shuttling rates of ERK and MEK. Using these parameters, we developed a kinetic simulation model consisting of the minimum essential members of the Ras/ERK MAPK cascade. This simple model reproduced essential features of the observed activation and nuclear translocation of ERK. In this model, the concentration of Raf significantly affected the levels of phospho-MEK and phospho-ERK upon stimulation. This prediction was confirmed experimentally by decreasing the level of Raf using the small interfering RNA technique. This observation verified the usefulness of the parameters collected in this study.

リンク情報
DOI
https://doi.org/10.1074/jbc.M509344200
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/16418172
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000236247100072&DestApp=WOS_CPL
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33646852421&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=33646852421&origin=inward
ID情報
  • DOI : 10.1074/jbc.M509344200
  • ISSN : 0021-9258
  • eISSN : 1083-351X
  • PubMed ID : 16418172
  • SCOPUS ID : 33646852421
  • Web of Science ID : WOS:000236247100072

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