Ligand-induced shedding of discoidin domain receptor 1.
Tyrosine kinases belonging to the discoidin domain receptor (DDR) family are activated upon stimulation with various types of collagen. In response to collagen treatment, immunoprecipitation of DDR1 with an antibody specific to the juxtamembrane region results in co-purification of a previously unrecognized tyrosine phosphorylated protein of 62 kDa molecular weight. Here, this protein is identified as C-terminal cleavage product of the full-length DDR1 receptor and a DDR1-specific shedding enzyme postulated. Shedding of DDR1 can be partially blocked by the furin inhibitor decanoyl-RVKR-chloromethylketone and completely inhibited by the hydroxamate-based inhibitor batimastat. The characteristic of the DDR1 sheddase to be blocked by batimastat suggests that it belongs to the membrane-bound matrix metalloproteinase or disintegrin and metalloproteinase family of proteases.
Vogel
Wolfgang F
WF
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Medical Science Building, Room 7334A, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. w.vogel@utoronto.ca
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D000070818:Discoidin Domain Receptors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D045683:Furin; D006801:Humans; D008024:Ligands; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D011975:Receptors, Mitogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013381:Subtilisins / Q000037:antagonists & inhibitors; D013876:Thiophenes / Q000494:pharmacology
D000906:Antibodies; D004791:Enzyme Inhibitors; D008024:Ligands; D020033:Protein Isoforms; D011975:Receptors, Mitogen; D013876:Thiophenes; D010649:Phenylalanine; D003094:Collagen; C080985:batimastat; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D013381:Subtilisins; D045683:Furin; D008666:Metalloendopeptidases