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RAF Kinases: Pathway, Modulation and Modeling

  • Kartonierter Einband
  • 96 Seiten
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The Ras/RAF/MEK/ERK cascade is a central cellular signal transduction pathway involved in cell proliferation, differentiation, and... Weiterlesen
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Beschreibung

The Ras/RAF/MEK/ERK cascade is a central cellular signal transduction pathway involved in cell proliferation, differentiation, and survival where RAF kinases are pivotal kinases implicated in cancer. The development of specific irreversible kinase inhibitors is a rewarding but difficult aim. A novel synthetic approach including a lyophilization step allowed us the synthesis of a diphenyl urea compound with an epoxide moiety (compound 1). Compound 1 possessed inhibitory activity in vitro. In cell culture experiments, a strong activation of the RAF signaling pathway was observed, an effect which is known from several other RAF kinase inhibitors and is here reported for the first time for a diphenyl urea compound. Furthermore, we developed a mathematical model of the Ras/RAF/MEK/ERK cascade demonstrating how stimuli induce different signal patterns and thereby different cellular responses, depending on the ratio between B-RAF and C-RAF. Additionally the effect of the tumor suppressor DiRas3 (also known as Noey2 or ARHI) on RAF signaling was studied. I could show that DiRas3 down-regulates the mitogenic pathway by inhibition of MEK.

Autorentext

I was born in Tehran-Iran but I moved to Austria at the age of six. After studying Chemical Engineering at the Technical University of Vienna, I moved to Göteborg--Sweden were I did my Master of Science in Bioinformatics. Thereafter I moved to Germany and did my doctorate in Bioinformatics at the University of Würzburg.

Produktinformationen

Titel: RAF Kinases: Pathway, Modulation and Modeling
Untertitel: New--Potentially Irreversible--Kinase Inhibitors, Computational Modeling of the Signaling Cascade, and the Effect of DiRas3 on RAF Signaling
Autor:
EAN: 9783639056655
ISBN: 978-3-639-05665-5
Format: Kartonierter Einband
Herausgeber: VDM Verlag
Genre: Biochemie & Biophysik
Anzahl Seiten: 96
Gewicht: 159g
Größe: H220mm x B150mm x T6mm
Veröffentlichung: 01.12.2008
Jahr: 2008
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