The differential amino acid requirement within osteopontin in α4 and α9 integrin-mediated cell binding and migration
| Autor: | Hong Yan Diao, Yoshinari Saito, Yosuke Nakayama, Shigeyuki Kon, Koyu Ito, Toshimitsu Uede, Masashi Kanayama, Junko Morimoto, Daisuke Kurotaki, Chiemi Kimura, Yutaka Matsui |
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| Rok vydání: | 2009 |
| Předmět: |
Integrin alpha4
Integrin CD18 CD49c Cell Line Collagen receptor Cell Movement Cricetinae Cell Adhesion otorhinolaryngologic diseases Animals Humans Amino Acid Sequence Amino Acids Cell adhesion Molecular Biology biology Chemistry Cell migration Molecular biology Recombinant Proteins Integrin alpha M Matrix Metalloproteinase 7 Mutation embryonic structures biology.protein Matrix Metalloproteinase 3 Osteopontin Integrin beta 6 sense organs Peptides Integrin alpha Chains Protein Binding |
| Zdroj: | Matrix Biology. 28:11-19 |
| ISSN: | 0945-053X |
| DOI: | 10.1016/j.matbio.2008.10.002 |
| Popis: | Osteopontin (OPN) contains at least two major integrin recognition domains, Arg159-Gly-Asp161 (RGD) and Ser162-Val-Val-Tyr-Gly-Leu-Arg168 (SVVYGLR), recognized by alphavbeta3 and alpha5beta1 and alpha4 and alpha9 integrins, respectively. OPN is specifically cleaved by thrombin and matrix metalloproteinase (MMP)-3 or MMP-7 at a position of Arg168/Ser169 (R/S) and Gly166/Leu167 (G/L), respectively. We in this study examined the requirement of residues within SVVYGLR for the alpha4 and alpha9 integrin recognition and how MMP-cleavage influences the integrin recognition. The residues, Val164, Tyr165, and Leu167 are critical for alpha4 and alpha9 integrin recognition in both cell adhesion and cell migration. The residue Arg168 is additionally required for alpha9 integrin recognition in cell adhesion and this explains why alpha9 integrin binds to only thrombin cleaved form of OPN. alpha4 integrin is able to bind to SVVYG (MMP-cleaved form of RAA OPN-N half), while alpha9 integrin is not, supporting the above notion that Arg168 is additionally required for alpha9 integrin-mediated cell adhesion. The residue Val163 is important for alpha4, but not for alpha9 integrin recognition in cell migration. Importantly, we found that the replacement of Arg168 by Ala (R168A mutant) induces the augmentation of cell migration via alpha4 and alpha9 integrins. |
| Databáze: | OpenAIRE |
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