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Osteopontin N-terminal domain contains a cryptic adhesive sequence recognized by alpha9beta1 integrin
L L Smith1, H K Cheung, L E Ling
1Department of Pathology, University of Washington, Seattle, Washington 98195, USA. ceci@u.washington.edu
The Journal of Biological Chemistry
|November 8, 1996
Summary
Thrombin cleavage of osteopontin (OPN) regulates its cell adhesion properties. This cleavage reveals a cryptic binding site, activating interactions with the alpha9beta1 integrin receptor, crucial in inflammation and remodeling.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Medicine
Background:
- Osteopontin (OPN) is an adhesive glycoprotein involved in inflammation and tissue remodeling.
- OPN contains key structural domains, including the RGD motif for cell attachment via integrins.
- Thrombin cleavage of OPN in vivo is suggested to be physiologically significant.
Purpose of the Study:
- To investigate the functional consequences of OPN cleavage by thrombin.
- To identify the specific OPN fragments and their roles in cell adhesion.
- To characterize the receptors mediating OPN-cell interactions.
Main Methods:
- Generation of glutathione S-transferase-OPN fusion proteins representing N- and C-terminal fragments.
- Comparison of cell adhesion capabilities of OPN fragments versus native OPN.
- Identification of cellular receptors involved in OPN-mediated adhesion.
Main Results:
- The N-terminal OPN fragment, containing the RGD domain, supports melanoma cell adhesion where native OPN does not.
- Thrombin cleavage of OPN alters its adhesive properties.
- A novel OPN receptor, identified as the alpha9beta1 integrin, recognizes a cryptic binding site on OPN.
Conclusions:
- Osteopontin's adhesive functions are regulated by thrombin-mediated cleavage.
- Thrombin cleavage exposes cryptic binding activities of OPN.
- The alpha9beta1 integrin is a key receptor for OPN, mediating interactions possibly revealed by cleavage.