Propolypeptide of von Willebrand factor is a novel ligand for very late antigen-4 integrin

Takashi Isobe, Tetsuya Hisaoka, Akira Shimizu, Mitsuhiro Okuno, Saburo Aimoto, Yoshikazu Takada, Yuji Saito, Junichi Takagi

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Abstract

We have previously reported that propolypeptide of von Willebrand factor (pp-vWF) promotes melanoma cell adhesion in a β1 integrin-dependent manner. In this report, we identified the α subunit of the cell adhesion receptor for pp-vWF as α4. Human leukemia cell lines that express α4β1 integrin (very late antigen-4, VLA-4), but not cell lines which lack VLA-4, attached well to pp-vWF substrate and these adhesions were completely inhibited by anti-α4 integrin monoclonal antibody HP2/1. Adhesion of mouse melanoma expressing α4 integrin was also inhibited by anti-mouse α4 mAb PS/2. Furthermore, transfection of human α4 cDNA into α4-Chinese hamster ovary cells resulted in an acquisition of adhesive activity to pp-vWF, indicating that pp-vWF is a ligand for VLA-4 integrin. Using a recombinant fragment of pp-vWF, the cell attachment site was shown to be located within amino acid residues 376-455 of pp-vWF. A series of synthetic peptides covering this region were tested for the ability to promote cell attachment and a 15- residue peptide designated T2-15 (DCQDHSF-SIVIETVQ, residues numbered 395- 409) promoted VLA-4 dependent cell adhesion. The peptide was also capable of inhibiting cell adhesion to pp-vWF, suggesting that this sequence represents the cell attachment site. By affinity chromatography using peptide T2-15- Sepharose, it was found that α4β1 integrin complex from extracts of surface iodinated B16 cells specifically bound to the peptide. These results strongly suggest that pp-vWF is a novel physiological ligand for VLA-4.

Original languageEnglish (US)
Pages (from-to)8447-8453
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number13
DOIs
StatePublished - Mar 28 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Isobe, T., Hisaoka, T., Shimizu, A., Okuno, M., Aimoto, S., Takada, Y., Saito, Y., & Takagi, J. (1997). Propolypeptide of von Willebrand factor is a novel ligand for very late antigen-4 integrin. Journal of Biological Chemistry, 272(13), 8447-8453. https://doi.org/10.1074/jbc.272.13.8447