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

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)19794-19800
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number32
DOIs
Publication statusPublished - Aug 8 1997
Externally publishedYes

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Integrins
Ligands
Vitronectin
Fibrinogen
von Willebrand Factor
Signal transduction
Focal Adhesions
Blocking Antibodies
Extracellular Matrix
Anti-Idiotypic Antibodies
Signal Transduction
Adhesion
Binding Sites
Mutation
Antibodies

ASJC Scopus subject areas

  • Biochemistry

Cite this

Changing ligand specificities of αvβ1 and αvβ3 integrins by swapping a short diverse sequence of the β subunit. / Takagi, Junichi; Kamata, Tetsuji; Meredith, Jere; Puzon-McLaughlin, Wilma; Takada, Yoshikazu.

In: Journal of Biological Chemistry, Vol. 272, No. 32, 08.08.1997, p. 19794-19800.

Research output: Contribution to journalArticle

Takagi, Junichi ; Kamata, Tetsuji ; Meredith, Jere ; Puzon-McLaughlin, Wilma ; Takada, Yoshikazu. / Changing ligand specificities of αvβ1 and αvβ3 integrins by swapping a short diverse sequence of the β subunit. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 32. pp. 19794-19800.
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