Priority Research Program of the German Research Foundation (DFG)
SPP 1190 - THE TUMOR - VESSEL INTERFACE
SPP 1190 - Projects
 
A. Abdollahi / P. Huber/
J. Debus
A. Acker-Palmer
T. Acker
R. Adams
F. Alves
H. Augustin
H. Beck / M. Conrad
G. Breier / B. Wielockx
P. Friedl
C. Bruns / P. Nelson
B. Homey / A. Müller-Homey
Ch. Klein
V. Orian-Rousseau / H. Ponta
K.T. Preissner
B. Sipos
J. Sleeman
P. Vajkoczy
 

 

Dr. Véronique Orian-Rousseau and Prof. Dr. Helmut Ponta

 

Institute of Toxicology and Genetics
Forschungszentrum Karlsruhe
P.O. Box 3640
D-76021 Karlsruhe, Germany
Tel.:++49 (0) 7247-82-4483
Fax.:++49 (0) 7247-82-3354

Lab Homepage

(Dr. Véronique Orian-Rousseau)


Veronique.Orian-Rousseau(at)itg.fzk.de

(Prof. Dr. Helmut Ponta)


Helmut.Ponta(at)itg.fzk.de
 
Molecular mechanisms of activation of tyrosine kinase receptors in angiogenesis
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.
 
- Relevant recent publications -

Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H: CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev 16: 3074-86, 2002

Khaldoyanidi S, Karakhanova S, Sleeman J, Herrlich P, Ponta H: CD44 variant-specific antibodies trigger hemopoiesis by selective release of cytokines from bone marrow macrophages. Blood 99: 3955-61, 2002.

Ponta H, Sherman L, Herrlich PA: CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4: 33-45, 2003

Machner MP, Frese S, Schubert WD, Orian-Rousseau V, Gherardi E, Wehland J, Niemann HH, Heinz DW:. Aromatic amino acids at the surface of InlB are essential for host cell invasion by Listeria monocytogenes. Mol Microbiol 48: 1525-36, 2003

Orian-Rousseau V, Mink S, Mengwasser J, HogenEsch H, Guo F, Thies WG, Hofmann M, Herrlich P, Ponta H: Genes up-regulated in a metastasizing human colon carcinoma cell line. Int J Cancer 113: 699-705, 2005

 
 
 
 
 
 
 

 
 
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Impressum | Last update: 06/26/2008