Changing ligand specificities of αvβ1 and αvβ3 integrins by swapping a short diverse sequence of the β subunit

Junichi Takagi, Tetsuji Kamata, Jere Meredith, Wilma Puzon-McLaughlin, Yoshikazu Takada

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105 引文 斯高帕斯(Scopus)

摘要

Integrins mediate signal transduction through interaction with multiple cellular or extracellular matrix ligands. Integrin αvβ3 recognizes fibrinogen, von Willebrand factor, and vitronectin, while αvβ1 does not. We studied the mechanisms for defining ligand specificity of these integrins by swapping the highly diverse sequences in the I domain-like structure of the β1 and β3 subunits. When the sequence CTSEQNC (residues 187-193) of β1 is replaced with the corresponding CYDMKTTC sequence of β3, the ligand specificity of αvβ1 is altered. The mutant (αvβ1-3-1), like αvβ3, recognizes fibrinogen, von Willebrand factor, and vitronectin (a gain-of- function effect). The αvβ1-3-1 mutant is recruited to focal contacts on fibrinogen and vitronectin, suggesting that the mutant transduces intracellular signals on adhesion. The reciprocal β3-1-3 mutation blocks binding of αvβ3 to these multiple ligands and to LM609, a function-blocking anti-αvβ3 antibody. These results suggest that the highly divergent sequence is a key determinant of integrin ligand specificity. Also, the data support a recent hypothetical model of the I domain of β, in which the sequence is located in the ligand binding site.

原文英語
頁(從 - 到)19794-19800
頁數7
期刊Journal of Biological Chemistry
272
發行號32
DOIs
出版狀態已發佈 - 八月 8 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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