Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Max-flanck-gesellschaft Zuer For{overscore (d)}erung Der

Birgit Millauer

Axel Ullrich

Werner Risau

Aviv Gazit

Alex Levitzki

Thomas Ciossek

The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention s based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.

Cell line comprising vector encoding truncated FLK-1 receptor

The present invention relates to MDK1 polypeptides, nucleic acids encoding such polypeptides, cells, tissues and animals containing such nucleic acids, antibodies to such polypeptides, assays utilizing such polypeptides, and methods relating to all of the foregoing. Methods for treatment, diagnosis, and screening are provided for diseases or conditions characterized by an abnormality in a signal transduction disorder. The signal transduction pathway involves an interaction between a MDK1 receptor tyrosine kinase and a receptor for the kinase. The MDK1 receptor tyrosine kinase may be truncated and lack a kinase domain and may be selected from the group consisting of MDK1.T1, MDK1.T2, MDK1.&#x394;1 and MDK1.&#x394;2.

Methods for diagnosis and treatment of MDK1 signal transduction disorders

The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and truncated Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.

Truncated Flk-1 receptor protein, methods of use and a recombinant vector containing a nucleotide encoding the truncated Flk-1 protein

MDK1 polypeptides

MDKI, a novel receptor tyrosine kinase

Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis

The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.

FLK-1 is a receptor for vascular endothelial growth factor

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San Francisco, CA, United States of America

Birgit Millauer