Der Beitrag von phosphoryliertem Rac1 (Ser-71) und daraus resultierender Anschaltung der NADPH Oxidase Signalwege zur Entwicklung von Darmkrebs

• Antragstellerin: Dr. Janett Schwarz
• Fachliche Zuordnung: Pharmakologie
• Förderung: Förderung von 2009 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 121821521

The Rho GTPases Rac1 and Rac2 are highly homologous and act as molecular switches to initiate downstream signaling. Phosphorylation of Rac1 at serine-71 is suspected to play a role in regulating effector binding and its activation. Both Rac1 and Rac2 regulate the activity of NADPH oxidases (Nox), which in turn generate Reactive Oxygen Species (ROS). Very little is known about the involved signals and the regulatory molecular machinery though. Nox proteins are found in virtually all tissues and have been implicated in such biological processes as cell proliferation, apoptosis, cell signaling, motility, and transcription. Evidence exists that Nox proteins play a key role in colon cancer formation. The studies proposed in this application focus on further investigation of - signaling pathways leading to phosphorylation of Rac1 at serine-71 (chapters A.2/D.1) - molecular mechanism by which phosphorylated Rac1/Rac2 affects Nox-dependent ROS generation (chapters A.3/D.2) - physiological relevance of phosphorylated Rac1 in mechanism of colon cancer (chapters A.4/D.3) The findings will help to understand the role of phosphorylated Rho GTPases Rac1 and Rac2 in regulating Nox proteins and their involvement in mechanisms promoting cancer formation and growth.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeberin: Céline Dermardirossian, Ph.D.