Fig. 8: Proposed model of VEGF-C-mediated lymphangiogenesis.
From: VEGFR2 is required for VEGF-C–VEGFR3–PI3Kα-mediated sprouting lymphangiogenesis
VEGF-C coordinates receptor abundance and signalling via VEGFR3 homodimers and VEGFR2/3 heterodimers. VEGF-C initially binds to its high-affinity receptor VEGFR3, inducing internalization and LEC proliferation. Concomitant VEGF-C-induced PI3Kα-dependent increase in VEGFR2 cell surface abundance shifts signalling toward VEGFR2/3 heterodimers, promoting vessel sprouting. This mechanism couples LEC proliferation with sprouting, ensuring adequate LEC numbers for functional lymphangiogenesis. While alternative modes of receptor cooperation cannot be excluded (denoted by?), functional and proximity-based data are most consistent with VEGF-C–induced VEGFR2/3 heterodimer signalling in vivo.
