Tuftsin binds neuropilin-1 through a sequence similar to that encoded by exon 8 of vascular endothelial growth factor

J Biol Chem. 2006 Mar 3;281(9):5702-10. doi: 10.1074/jbc.M511941200. Epub 2005 Dec 21.

Abstract

Tuftsin, Thr-Lys-Pro-Arg (TKPR), is an immunostimulatory peptide with reported nervous system effects as well. We unexpectedly found that tuftsin and a higher affinity antagonist, TKPPR, bind selectively to neuropilin-1 and block vascular endothelial growth factor (VEGF) binding to that receptor. Dimeric and tetrameric forms of TKPPR had greatly increased affinity for neuropilin-1 based on competition binding experiments. On endothelial cells tetrameric TKPPR inhibited the VEGF(165)-induced autophosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) even though it did not directly inhibit VEGF binding to VEGFR-2. Homology between exon 8 of VEGF and TKPPR suggests that the sequence coded for by exon 8 may stabilize VEGF binding to neuropilin-1 to facilitate signaling through VEGFR-2. Given the overlap between processes involving neuropilin-1 and tuftsin, we propose that at least some of the previously reported effects of tuftsin are mediated through neuropilin-1.

MeSH terms

  • Amino Acid Sequence*
  • Animals
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Exons*
  • Fluorescent Dyes / metabolism
  • Humans
  • Immunologic Factors / genetics
  • Immunologic Factors / metabolism*
  • Microbubbles
  • Molecular Structure
  • Neuropilin-1 / genetics
  • Neuropilin-1 / metabolism*
  • Peptides / genetics
  • Peptides / metabolism*
  • Protein Binding
  • Radioligand Assay
  • Signal Transduction / physiology
  • Tuftsin / genetics
  • Tuftsin / metabolism*
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Fluorescent Dyes
  • Immunologic Factors
  • Peptides
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1
  • Vascular Endothelial Growth Factor Receptor-2
  • Tuftsin