Vascular endothelial growth factor-like protein from orf viruses binds and activates mammalian VEGF receptor-2, and uses thereof
AssigneesUniversity of Otago, Ludwig Institute for Cancer Research
InventorsLyn M. Wise, Andrew A. Mercer, Loreen J. Savory, Stephen B. Fleming, Steven A. Stacker
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Abstract
The invention is based on the discovery that a viral VEGF-like protein from the orf virus strain NZ2 and from the orf virus strain NZ10 is capable of binding to the extracellular domain of the VEGF receptor-2 to form bioactive complexes which mediate useful cellular responses and/or antagonize undesired biological activities. Disclosed are methods which stimulate or inhibit these biological activities, methods for therapeutic applications and antagonists of ORFV2-VEGF and/or NZ10.
Claims17
A method for activation of VEGF receptor 2, comprising the step of exposing cells bearing said receptor to an effective receptor activating dose of a polypeptide selected from the group consisting of ORFV2-VEGF and NZ10.
A method for specific activation of VEGF receptor 1:
- comprising the step of exposing cells bearing said receptor to an effective receptor activating dose of a polypeptide selected from the group consisting of ORFV2-VEGF and NZ10.
A method for stimulating proliferation of endothelial or mesodermal cells, wherein the cells bear VEGF receptor 2, comprising activating the receptor via exposing said endothelial or mesodermal cells to an effective receptor-activating amount of a polypeptide selected from the group consisting of ORFV2-VEGF and NZ10, thereby stimulating the proliferation of the cells.
A method for modulating vascular permeability, comprising the step of administering an effective vascular permeability-modulating amount of an NZ10 polypeptide.
A method for stimulating proliferation of endothelial or mesodermal cells, comprising the step of exposing the endothelial or mesodermal cells to an effective endothelial or mesodermal cell proliferation-stimulating amount of a NZ10 polypeptide.
A method for modulating permeability of a vascular system in an animal in need thereof, wherein endothelial cells of the vascular system bear VEGF receptor 2, comprising activating the receptor via exposing said endothelial cells to an effective receptor-activating amount of a polypeptide selected from the group consisting of ORFV2-VEGF and NZ10, thereby modulating vascular permeability.
Dependencies are inferred from the claim text.