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Proteolytic Cleavages in the VEGF Family: Generating Diversity among Angiogenic VEGFs, Essential for the Activation of Lymphangiogenic VEGFs

Künnapuu, Jaana ; Bokharaie, Honey ; Jeltsch, Michael

Biology (Basel, Switzerland), 2021-02, Vol.10 (2), p.167 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Proteolytic Cleavages in the VEGF Family: Generating Diversity among Angiogenic VEGFs, Essential for the Activation of Lymphangiogenic VEGFs
Autor: Künnapuu, Jaana ; Bokharaie, Honey ; Jeltsch, Michael
Assuntos: Angiogenesis ; Binding sites ; Blood platelets ; Cardiovascular system ; Cathepsin D ; Embryogenesis ; Extracellular matrix ; Growth factors ; Heparan sulfate ; Immune response ; Lymphatic system ; Lymphedema ; Plasmin ; PlGF ; Prostate ; Prostate-specific antigen ; Proteins ; Proteolysis ; Receptor mechanisms ; Review ; Thrombin ; Vascular endothelial growth factor ; vascular endothelial growth factors (VEGFs) ; VEGF-A ; VEGF-B ; VEGF-C ; VEGF-D ; Vertebrates ; Wound healing
É parte de: Biology (Basel, Switzerland), 2021-02, Vol.10 (2), p.167
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
Descrição: Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph-angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. At least five different proteases mediate the activating cleavage of VEGF-C: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the "mature" growth factors, which differ in affinity and receptor activation potential. The "default" VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D, and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by distinct proteases. During embryonic development, ADAMTS3 activates VEGF-C. The other activating proteases are likely important for non-developmental lymphangiogenesis during, e.g., tissue regeneration, inflammation, immune response, and pathological tumor-associated lymphangiogenesis. The better we understand these events at the molecular level, the greater our chances of developing successful therapies targeting VEGF-C and VEGF-D for diseases involving the lymphatics such as lymphedema or cancer.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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Proteolytic Cleavages in the VEGF Family: Generating Diversity among Angiogenic VEGFs, Essential for the Activation of Lymphangiogenic VEGFs

Künnapuu, Jaana ; Bokharaie, Honey ; Jeltsch, Michael

Switzerland: MDPI AG

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