KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

Vascular endothelial growth factor-C (VEGF-C) acts primarily on endothelial cells, but also on non-vascular targets, e.g. in the CNS and immune system. Here we describe a novel, unique VEGF-C form in the human reproductive system produced via cleavage by kallikrein-related peptidase 3 (KLK3), aka prostate-specific antigen (PSA). KLK3 activated VEGF-C specifically and efficiently through cleavage at a novel N-terminal site. We detected VEGF-C in seminal plasma, and sperm liquefaction occurred concurrently with VEGF-C activation, which was enhanced by collagen and calcium binding EGF domains 1 (CCBE1). After plasmin and ADAMTS3, KLK3 is the third protease shown to activate VEGF-C. Since differently activated VEGF-Cs are characterized by successively shorter N-terminal helices, we created an even shorter hypothetical form, which showed preferential binding to VEGFR-3. Using mass spectrometric analysis of the isolated VEGF-C-cleaving activity from human saliva, we identified cathepsin D as a protease that can activate VEGF-C as well as VEGF-D.
Originalspråkengelska
Artikelnummer44478
TidskrifteLife
Volym8
Antal sidor30
ISSN2050-084X
DOI
StatusPublicerad - 17 maj 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 3111 Biomedicinska vetenskaper
  • 1182 Biokemi, cell- och molekylärbiologi
  • 1184 Genetik, utvecklingsbiologi, fysiologi

Citera det här