%0 Journal Article %J eLife %D 2019 %T KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D %A Jha, Sawan Kumar %A Rauniyar, Khushbu %A Chronowska, Ewa %A Mattonet, Kenny %A Maina, Eunice Wairimu %A Koistinen, Hannu %A Stenman, Ulf-HÃ¥kan %A Alitalo, Kari %A Jeltsch, Michael %K cancer biology %K Cathepsin D %K kallikrein-related peptidases %K KLK3/PSA %K Lymphangiogenesis %K mouse %K VEGF-C %K VEGF-D %X 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. %B eLife %V 8 %P e44478 %8 2019/05/17/ %@ 2050-084X %G eng %U https://elifesciences.org/articles/44478 %! eLife %0 Journal Article %J Annals of Anatomy - Anatomischer Anzeiger %D 2018 %T Key molecules in lymphatic development, function, and identification %A Jha, SK %A Rauniyar, K %A Jeltsch, M %X While both blood and lymphatic vessels transport fluids and thus share many similarities, they also show functional and structural differences, which can be used to differentiate them. Specific visualization of lymphatic vessels has historically been and still is a pivot point in lymphatic research. Many of the proteins that are investigated by molecular biologists in lymphatic research have been defined as marker molecules, i.e. to visualize and distinguish lymphatic endothelial cells (LECs) from other cell types, most notably from blood vascular endothelial cells (BECs) and cells of the hematopoietic lineage.Among the factors that drive the developmental differentiation of lymphatic structures from venous endothelium, Prospero homeobox protein 1 (PROX1) is the master transcriptional regulator. PROX1 maintains lymphatic identity also in the adult organism and thus is a universal LEC marker. Vascular endothelial growth factor receptor-3 (VEGFR-3) is the major tyrosine kinase receptor that drives LEC proliferation and migration. The major activator for VEGFR-3 is vascular endothelial growth factor-C (VEGF-C). However, before VEGF-C can signal, it needs to be proteolytically activated by an extracellular protein complex comprised of Collagen and calcium binding EGF domains 1 (CCBE1) protein and the protease A disintegrin and metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3).This minireview attempts to give an overview of these and a few other central proteins that scientific inquiry has linked specifically to the lymphatic vasculature. It is limited in scope to a brief description of their main functions, properties and developmental roles. %B Annals of Anatomy - Anatomischer Anzeiger %V 219 %P 25 - 34 %8 2018/09/01/ %@ 09409602 %G eng %U http://linkinghub.elsevier.com/retrieve/pii/S0940960218300712 %9 review %! Ann Anat %& 25 %R 10.1016/j.aanat.2018.05.003