Identification of motifs in the fasciclin domains of the transforming growth factor-β-induced matrix protein βig-h3 that interact with the αvβ5 integrin

Jung Eun Kim, Ha Won Jeong, Ju Ock Nam, Byung Heon Lee, Je Yong Choi, Rang Woon Park, Jae Yong Park, In San Kim

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

βig-h3 is a TGF-β-induced matrix protein known to mediate the adhesion of several cell types. In this study, we found that all four of the fas-1 domains in βig-h3 mediate MRC-5 fibroblast adhesion and that this was specifically inhibited by a function-blocking monoclonal antibody specific for the αvβ5 integrin. Using deletion mutants of the fourth fas-1 domain revealed the MRC-5 cell adhesion motif (denoted the YH motif) is located in amino acids 548-614. Experiments with substitution mutants showed that tyrosine 571, histidine 572, and their flanking leucine and isoleucine amino acids, which are all highly conserved in many fas-1 domains, are essential for mediating MRC-5 cell adhesion. A synthetic 18-amino acid peptide encompassing these conserved amino acids could effectively block MRC-5 cell adhesion to βig-h3. Using HEK293 cells stably transfected with the β5 integrin cDNA, we confirmed that the αvβ5 integrin is a functional receptor for the YH motif. In conclusion, we have identified a new αvβ5 integrininteracting motif that is highly conserved in the fas-1 domains of many proteins. This suggests that fas-1 domain-containing proteins may perform their biological functions by interacting with integrins.

Original languageEnglish
Pages (from-to)46159-46165
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number48
DOIs
Publication statusPublished - 2002 Nov 29
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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