FIG. 6.

Proposed model of KSHV-induced lymphatic reprogramming of endothelial cells. KSHV infection of endothelial cells induces the secretion of a soluble factor that activates the gp130 receptor. Activation of the gp130 receptor activates JAK2, which directly phosphorylates and activates STAT3. Downstream of gp130, JAK2 also promotes the activation of PI3K to phosphorylate Akt. Prox1 is induced downstream of the PI3K/Akt pathway and regulates VEGFR-3 induction and podoplanin expression. STAT3 regulates gp130 induction, and its persistent activation controls a positive autoregulatory loop of the entire signaling pathway. Arrows with solid lines, direct regulation; arrows with dashed lines, indirect regulation of the target.