Molecular mechanisms of activation of tyrosine kinase receptors in angiogenesis

• Applicant: Professorin Dr. Véronique Orian-Rousseau
• Subject Area: Pathology
• Term: from 2006 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 22052911

Recent evidence revealed that the activation of several receptor tyrosine kinases (RTK) by their ligands is dependent on accessory proteins. E.G. the Met receptor can make use of integrins to enhance signalling or of members of the plexin family to expand its ligand repertoire or on CD44v6 that enables receptor activation as well as transmission of signals. Our main goal in this grant application is the molecular understanding of the activation of RTKs such as VEGF-Rs, Met and EGF-Rs, that play decisive roles in angiogenesis. All these RTKs are candidates to require a CD44 isoform for their activation. We will identify which isoforms of CD44 are required and how they cooperate with the RTKs. Furthermore we will try to identify critical sequences in the CD44 and RTK proteins that are required for their interaction. Based on this information we plan to develop tools to interfere specifically with the interaction and to inhibit angiogenesis. In in vivo models of angiogenesis we will sort out at which step of angiogenesis the individual RTKs and the different CD44 isoforms are acting.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1190: The Tumour-Vessel Interface
• Participating Person: Professor Dr. Helmut Ponta