Figure 10. Schematic representation of the primary structure of proVEGF-C, its activating proteases and receptors R2 and R3.

Upon synthesis and translocation into the Golgi network, proVEGF-C is processed at HSIIRR₂₁₄, dividing it into N-terminal (VEGF-C) and C-terminal polypeptides. The cleavage of proVEGF-C can also occurs via cell surface-attached convertases (PCs). Interaction of mature VEGF-C (wt) with the receptors VEGF/R3 and VEGF/R2 leads to Akt/ERK activation and functions. Mutation of the cleavage site of proVEGF-C (mut) prevents Akt/ERK activation and cell proliferation.