Fig. 2.

RCAN1 in the regulatory network of VEGF-VEGFR2 signaling. VEGF induces RCAN1.1 upregulation via YAP1-TEF3 activation which is possibly mediated by neuropilin and VEGFR2. VEGF stimulation-induced VEGFR2 phosphorylation activates PLCγ, which cleavages PIP2 into IP3. IP3 enhances the release of Ca²⁺ contributing to the activation of calcineurin/NFAT signaling, which promotes RCAN1.4 expression. On the other hand, both RCAN1.1 and RCAN1.4 participates in VEGF-VEGFR2 signaling via inhibiting calcineurin-NFAT signaling-mediated RCAN1.4 expression. RCAN1.4 facilitates VEGFR2 internalisation followed by proteolytic degradation, and facilitatesVEGFR2 phosphorylation possibly mediated by integrin αvβ5 complex. The arrowhead stands for positive regulation, while T-shaped end stands for inhibition. Dotted line stands for possible signaling pathways. P within the red circle represents the phosphorylation form of VEGFR2