The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis

The Journal of Clinical Investigation
Geraldine SiegfriedAbdel-Majid Khatib

Abstract

The secretory factor VEGF-C has been directly implicated in various physiological processes during embryogenesis and human cancers. However, the importance of the conversion of its precursor proVEGF-C to mature VEGF-C in tumorigenesis, and vessel formation and the identity of the protease(s) that regulate these processes is/are not known. The intracellular processing of proVEGF-C that occurs within the dibasic motif HSIIRR(227)SL suggests the involvement of the proprotein convertases (PCs) in this process. In addition, furin and VEGF-C were found to be coordinately expressed in adult mouse tissues. Cotransfection of the furin-deficient colon carcinoma cell line LoVo with proVEGF-C and different PC members revealed that furin, PC5, and PC7 are candidate VEGF-C convertases. This finding is consistent with the in vitro digestions of an internally quenched synthetic fluorogenic peptide mimicking the cleavage site of proVEGF-C ((220)Q-VHSIIRR downward arrow SLP(230)). The processing of proVEGF-C is blocked by the inhibitory prosegments of furin, PC5, and PACE4, as well as by furin-motif variants of alpha2-macroglobulin and alpha1-antitrypsin. Subcutaneous injection of CHO cells stably expressing VEGF-C into nude mice enhanced angiog...Continue Reading

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Citations

Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Tao YangBrendan Lee
Jan 7, 2011·The Journal of Biological Chemistry·Estelle RousseletNabil G Seidah
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Methods Mentioned

BETA
PCR
transfections
immunoprecipitation
immunoprecipitations
transfection

Software Mentioned

GraFit

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