Osteopontin N-terminal domain contains a cryptic adhesive sequence recognized by alpha(9)beta(1) integrin

被引:222
作者
Smith, LL
Cheung, HK
Ling, LE
Chen, J
Sheppard, D
Pytela, R
Giachelli, CM
机构
[1] UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195
[2] BIOGEN INC,DEPT BIOL RES,CAMBRIDGE,MA 02142
[3] UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143
[4] SAN FRANCISCO GEN HOSP,LUNG BIOL CTR,SAN FRANCISCO,CA 94110
关键词
D O I
10.1074/jbc.271.45.28485
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Osteopontin is an adhesive glycoprotein implicated in numerous diseases associated with inflammation and remodeling. There are several structural domains in osteopontin that are of particular interest. The RGD motif is a cell attachment sequence shown to be critical for cell adhesion through alpha(v)-containing integrins. In close proximity to the RGD domain is the thrombin cleavage site. Previous observations suggest that thrombin cleavage of osteopontin occurs in vivo and may be physiologically important. To study the functional significance of osteopontin cleavage by thrombin, we made glutathione S-transferase-osteopontin fusion proteins. These proteins contain either the N- or C-terminal domains expected to be formed following thrombin cleavage at the Arg(169)Ser(170) peptide bond, We compared these osteopontin fragments with native osteopontin in their ability to support adhesion of several different cell lines and identified the receptors mediating these interactions. Our data show that the N-terminal osteopontin fragment, which contains the RGD domain, supports adhesion of a melanoma cell line that is unable to bind native osteopontin. This suggests that osteopontin adhesive interactions may be regulated by thrombin cleavage. We also demonstrate that osteopontin contains a cryptic binding activity, which can be recognized by a novel osteopontin receptor. This receptor has been identified as the alpha(9) beta(1) integrin.
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页码:28485 / 28491
页数:7
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