Die proteolytische Aktivierung des Vaskulären Endothelzellwachstumsfaktors-C

Translated title of the contribution: The Proteolytic Activation of Vascular Endothelial Growth Factor-C

Research output: Contribution to journalReview ArticleScientificpeer-review

Abstract

The enzymatic cleavage of the protein backbone (proteolysis) is integral to many biological processes, such as for the breakdown of proteins in the digestive system. Specific proteolytic cleavages are also used to turn on or off the activity of proteins. For example, lymph­angiogenic vascular endothelial growth factor C (VEGF-C) is synthesized as a precursor molecule that must be converted to a mature form by the enzymatic removal of C- and N-terminal propeptides before it can bind and activate its receptors. The constitutive C-terminal cleavage is mediated by proprotein convertases such as furin. The subsequent activating cleavage can be mediated by at least 4 different proteinases: by plasmin, ADAMTS3, prostate-specific antigen (PSA) and cathepsin D. Processing by different proteinases results in distinct forms of "mature" VEGF-C that differ in their affinity and their receptor activation potential. The CCBE1 protein regulates the activating cleavage of VEGF-C by ADAMTS3 and PSA, but not by plasmin.
During embryonic development of the lymphatic system, VEGF-C is activated primarily by the ADAMTS3 proteinase. In contrast, it is believed that plasmin is responsible for wound-healing lymphangiogenesis and PSA for tumor-associated pathological lymphangio­genesis. Cathepsin D has also been implicated in tumor lymphangiogenesis. In addition, cathepsin D contained in saliva might activate latent VEGF-C upon wound licking, thereby accelerating wound healing. The molecular details of proteolytic activation of VEGF-C have only recently been extensively explored, and it is likely that not all activating proteinases are known as yet. It appears that the activity of VEGF-C is regulated for different specific functions by different proteinases.
Although VEGF-C clearly plays a pivotal role for tumor progression and metastasis in experimental animal studies, the relevance of most correlative studies on the role of VEGF-C in human cancers has been quite limited until now, also due to the lack of methods for differentiating between inactive and active forms of VEGF-C
Original languageGerman
JournalLymphologie in Forschung und Praxis
Volume23
Issue number2
Pages (from-to)88
Number of pages98
ISSN1433-5255
Publication statusPublished - 18 Dec 2019
MoE publication typeA2 Review article in a scientific journal

Fields of Science

  • 317 Pharmacy

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