KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D.
Elife
; 82019 05 17.
Article
en En
| MEDLINE
| ID: mdl-31099754
ABSTRACT
Vascular endothelial growth factor-C (VEGF-C) acts primarily on endothelial cells, but also on non-vascular targets, for example 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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Calicreínas
/
Catepsina D
/
Antígeno Prostático Específico
/
Factor C de Crecimiento Endotelial Vascular
/
Factor D de Crecimiento Endotelial Vascular
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Elife
Año:
2019
Tipo del documento:
Article