Ligands for discoidin domain receptor tyrosine kinases and complexes thereof

A peptide derived from the binding domain of a discoidin domain receptor tyrosine kinase that interacts with a collagen, or interacts with Shc or a protein containing a PDZ domain.

A molecule derived from the binding domain of collagen that interacts with a discoidin domain receptor tyrosine kinase.

A method for evaluating a compound for its ability to modulate a DDR-mediated signaling pathway, comprising the steps of:

• (a) reacting a collagen, and at least one discoidin domain receptor tyrosine kinase protein, or an isoform or a part of the protein, and a test substance, wherein the collagen and discoidin domain receptor tyrosine kinase protein are selected so that they bind to form a collagen-discoidin domain receptor tyrosine kinase protein complex;
• and
• (b) comparing to a control in the absence of the substance to determine the effect of the substance.

A method for identifying a substance which affects a DDR receptor tyrosine kinase-mediated signaling pathway in a cell, comprising (a) reacting a collagen or part thereof, and at least one discoidin domain receptor tyrosine kinase protein, or an isoform or a part of the protein, and a test substance, wherein the collagen and discoidin domain receptor tyrosine kinase protein are selected so that they bind to form a collagen-discoidin domain receptor tyrosine kinase protein complex, under conditions which permit the formation of collagen-discoidin domain receptor tyrosine kinase protein complexes, and (b) assaying for complexes, for free substance, for non-complexed collagen, or for activation of the protein.

A method for up-regulating MMP-1 expression in a cell comprising administering a discoidin domain receptor 2 or an oligomer thereof.