Kuvaus
| Alkuperäiskieli | englanti |
|---|---|
| Artikkeli | 44478 |
| Lehti | eLife |
| Vuosikerta | 8 |
| Sivumäärä | 30 |
| ISSN | 2050-084X |
| DOI - pysyväislinkit | |
| Tila | Julkaistu - 17 toukokuuta 2019 |
| OKM-julkaisutyyppi | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu |
Tieteenalat
- 3111 Biolääketieteet
- 1182 Biokemia, solu- ja molekyylibiologia
- 1184 Genetiikka, kehitysbiologia, fysiologia
Lainaa tätä
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KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D. / Jha, Sawan Kumar; Rauniyar, Khusbu; Chronowska, Ewa; Mattonet, Kenny; Maina, Eunice; Koistinen, Hannu; Stenman, Ulf Håkan; Alitalo, Kari; Jeltsch, Michael.
julkaisussa: eLife, Vuosikerta 8, 44478, 17.05.2019.Tutkimustuotos: Artikkelijulkaisu › Artikkeli › Tieteellinen › vertaisarvioitu
TY - JOUR
T1 - KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D
AU - Jha, Sawan Kumar
AU - Rauniyar, Khusbu
AU - Chronowska, Ewa
AU - Mattonet, Kenny
AU - Maina, Eunice
AU - Koistinen, Hannu
AU - Stenman, Ulf Håkan
AU - Alitalo, Kari
AU - Jeltsch, Michael
PY - 2019/5/17
Y1 - 2019/5/17
N2 - 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.
AB - 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.
KW - 3111 Biomedicine
KW - vascular biology
KW - Reproductive Biology
KW - CANCER METASTASIS
KW - 1182 Biochemistry, cell and molecular biology
KW - VEGF-C
KW - VEGF-D
KW - Prostate-specific antigen
KW - Cathepsin D
KW - CCBE1
KW - 1184 Genetics, developmental biology, physiology
KW - angiogenesis
KW - lymphangiogenesis
U2 - 10.7554/eLife.44478
DO - 10.7554/eLife.44478
M3 - Article
VL - 8
JO - eLife
JF - eLife
SN - 2050-084X
M1 - 44478
ER -