A Novel Consensus Motif in Fibronectin Mediates Dipeptidyl Peptidase IV Adhesion and Metastasis

Hung Chi Cheng, Mossaad Abdel-Ghany, Bendicht U. Pauli

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113 Citations (Scopus)

Abstract

Lung endothelial dipeptidyl peptidase IV (DPPIV/CD26) is a vascular address for cancer cells decorated with cell-surface polymeric fibronectin (poly-FN). Here, we identified the DPPIV-binding sites in FN and examined the effect of binding site peptides on DPPIV/poly-FN adhesion and metastasis. Using proteolytic fragments and maltose-binding protein fusion proteins that together span full-length FN, we found DPPIV-binding sites in type III repeats 13, 14, and 15 (FNIII13, -14, and -15, respectively). DPPIV binding was mediated by the consensus motif T(I/L)TGLX(P/R)G(T/V)X and was confirmed by swapping this motif in FNIII13, -14, and -15 with the corresponding region in FNIII12, which did not bind DPPIV. DPPIV binding was lost in swapped FNIII13, -14, and -15 and gained in swapped FNIII12 (FNIII12(14)). Peptides containing the DPPIV-binding domain of FNIII14 blocked DPPIV/poly-FN adhesion and impeded pulmonary metastasis. This study adds to the classes of cell-surface adhesion receptors for FN and will help in the further characterization of the functional implications of the DPPIV/poly-FN adhesion in metastasis and possibly in cell-mediated immunity involving DPPIV-expressing lymphocytes.

Original languageEnglish
Pages (from-to)24600-24607
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number27
DOIs
Publication statusPublished - 2003 Jul 4

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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