Mapping of the cryptic integrin-binding site in osteopontin suggests a new mechanism by which thrombin can regulate inflammation and tissue repair.
The integrin alpha9beta1 mediates neutrophil migration across several ligands that are enriched at sites of inflammation. In one of these ligands, the acidic phosphoprotein osteopontin, the alpha9beta1 binding site is cryptic, but is revealed after thrombin cleavage. We have recently mapped the alpha9beta1 binding site in osteopontin to the linear peptide sequence, SVVYGLR, immediately adjacent to the thrombin cleavage site. Interestingly, this site is also adjacent to a sequence (RGD) through which five other integrins bind to osteopontin. These findings suggest a novel mechanism by which thrombin can modulate integrin signaling at sites of tissue injury.
Lung Biology Center, Department of Medicine, University of California, San Francisco, CA, USA.
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Yokasaki
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Sheppard
D001665:Binding Sites; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D053495:Osteopontin; D010449:Peptide Mapping; D012795:Sialoglycoproteins / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism* / Q000502:physiology*
D016023:Integrins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C113256:integrin alpha 9 beta 1; D053495:Osteopontin; D013917:Thrombin