title: Tuftsin binds neuropilin-1 through a sequence similar to that encoded by exon 8 of vascular endothelial growth factor.
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.
authors.affiliation: Ernst Felder Laboratories, Bracco Research USA, 305 College Road East, Princeton, NJ 08540, USA. mvonwron@bru.bracco.com
authors.forename: Mathew A
authors.initials: MA
authors.lastname: von Wronski
authors.forename: Natarajan
authors.initials: N
authors.lastname: Raju
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Pillai
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Bogdan
authors.forename: Edmund R
authors.initials: ER
authors.lastname: Marinelli
authors.forename: Palaniappa
authors.initials: P
authors.lastname: Nanjappan
authors.forename: Kondareddiar
authors.initials: K
authors.lastname: Ramalingam
authors.forename: Thangavel
authors.initials: T
authors.lastname: Arunachalam
authors.forename: Steve
authors.initials: S
authors.lastname: Eaton
authors.forename: Karen E
authors.initials: KE
authors.lastname: Linder
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Sibylle
authors.initials: S
authors.lastname: Pochon
authors.forename: Michael F
authors.initials: MF
authors.lastname: Tweedle
authors.forename: Adrian D
authors.initials: AD
authors.lastname: Nunn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005091:Exons; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism*; D045423:Microbubbles; D015394:Molecular Structure; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011869:Radioligand Assay; D015398:Signal Transduction / Q000502:physiology; D014405:Tuftsin / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D007155:Immunologic Factors; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D014405:Tuftsin