Artery- and vein-specific proteins and uses therefor

A method for identifying an agent that enhances an interaction of EphrinB2 and EphB4, comprising:

• (a) combining:
• (1) an EphrinB2 protein or at least a portion thereof sufficient to interact with an EphB4 protein,
• (2) an EphB4 or at least a portion thereof sufficient to interact with said EphrinB2 protein, and
• (3) an agent,
• under conditions appropriate for interaction between said EphrinB2 and EphB4 proteins in the presence of said agent;
• (b) determining the extent to which said EphrinB2 and EphB4 proteins interact;
• (c) comparing the extent of interaction determined in (b) with the extent to which interaction of said EphrinB2 and EphB4 proteins occurs in the absence of the agent;
• wherein if the extent to which of the interaction of said EphrinB2 and EphB4 proteins is greater in the presence of the agent than in the absence of the agent, the agent is one which enhances interaction of EphrinB2 and EphB4;
• and
• (d) for an agent that enhances said interaction, further assessing the ability of said agent to enhance blood vessel formation.

A method for identifying an agent having an anti-angiogenic activity, comprising

• (a) combining
• an EphrinB2 protein, or a portion thereof that interacts with EphB4, and an EphB4 protein, or a portion thereof that interacts with EphrinB2,
• wherein said EphrinB2 and EphB4 proteins interact to form a ligand-receptor complex;
• (b) determining if a test agent can interfere with a function of said ligand-receptor complex;
• and
• (c) for said test agent that interferes with said ligand-receptor complex, administering said agent to a nonhuman animal and measuring the anti-angiogenic activity, if any, of said agent.

A method for identifying an agent having an anti-angiogenic activity comprising:

• (a) contacting
• (i) cells expressing an EphB4 protein, which cells differentiate or maintain a venous phenotype in a manner dependent on the activity of the EphB4 protein, and
• (ii) a test agent;
• and
• (b) determining if the agent can interfere with the ability of said EphB4 protein to transduce a signal that affects said venous phenotypes.

A method for identifying an agent having an anti-angiogenic activity comprising:

• (a) contacting
• (i) cells expressing an EphrinB2 protein, which cells differentiate or maintain an arterial phenotype in a manner dependent on the activity of the EphrinB2 protein, and
• (ii) a test agent;
• and
• (b) determining if the agent can interfere with the ability of said EphrinB2 protein to transduce a signal that affects said arterial phenotype.

A method for evaluating the effect of an agent on angiogenesis comprising:

• (a) identifying or obtaining an agent that exhibits one or more of the following properties:
• (i) interferes with the ability of an EphB4 protein to transduce a signal that affects a venous phenotype of an endothelial cell;
• (ii) interferes with the ability of an EphrinB2 protein to transduce a signal that affects an arterial phenotype of an endothelial cell;
• (iii) decreases the extent of interaction between an EphB4 polypeptide and an EphrinB2 polypeptide;
• and
• (b) evaluating the effect of said agent on angiogenesis in a non-human animal.