The differential amino acid requirement within osteopontin in α4 and α9 integrin-mediated cell binding and migration

Koyu Ito, Shigeyuki Kon, Yosuke Nakayama, Daisuke Kurotaki, Yoshinari Saito, Masashi Kanayama, Chiemi Kimura, Hong Yan Diao, Junko Morimoto, Yutaka Matsui, Toshimitsu Uede

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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 αvβ3 and α5β1 and α4 and α9 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 α4 and α9 integrin recognition and how MMP-cleavage influences the integrin recognition. The residues, Val164, Tyr165, and Leu167 are critical for α4 and α9 integrin recognition in both cell adhesion and cell migration. The residue Arg168 is additionally required for α9 integrin recognition in cell adhesion and this explains why α9 integrin binds to only thrombin cleaved form of OPN. α4 integrin is able to bind to SVVYG (MMP-cleaved form of RAA OPN-N half), while α9 integrin is not, supporting the above notion that Arg168 is additionally required for α9 integrin-mediated cell adhesion. The residue Val163 is important for α4, but not for α9 integrin recognition in cell migration. Importantly, we found that the replacement of Arg168 by Ala (R168A mutant) induces the augmentation of cell migration via α4 and α9 integrins.

Original languageEnglish
Pages (from-to)11-19
Number of pages9
JournalMatrix Biology
Volume28
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1
Externally publishedYes

Keywords

  • Cell adhesion
  • Cell migration
  • Osteopontin
  • α4 Integrin
  • α9 Integrin

ASJC Scopus subject areas

  • Molecular Biology

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  • Cite this

    Ito, K., Kon, S., Nakayama, Y., Kurotaki, D., Saito, Y., Kanayama, M., Kimura, C., Diao, H. Y., Morimoto, J., Matsui, Y., & Uede, T. (2009). The differential amino acid requirement within osteopontin in α4 and α9 integrin-mediated cell binding and migration. Matrix Biology, 28(1), 11-19. https://doi.org/10.1016/j.matbio.2008.10.002