Fig. 1.

Schematic of FGF and VEGF signaling network. Signaling is induced by the growth factors binding to their receptors, culminating with phosphorylation of ERK, through the MAPK cascade. MAPK signaling is initiated through the activation of Raf and FRS2 by VEGF and FGF, respectively. The FGF:HSGAG:FGFR1 complex dimerizes and leads to phosphorylation of FRS2 (pFRS2). VEGF binds VEGFR2 to activate Ras, forming Ras-GTP, which further activates Raf (aRaf). Both aRaf and pFRS2 are able to phosphorylate MEK at two sites, and doubly phosphorylated MEK (ppMEK) further phosphorylates ERK. ppERK provides negative feedback on the FGF pathway, as it promotes ubiquitination of FRS2 (FRS2u)