Figure 2.

Factor XII signaling pathways leading to angiogenesis. Factor XII (FXII) binds to uPAR domain 2 (D2) to set up a signaling cascade resulting in endothelial cell growth, proliferation, and angiogenesis. High‐molecular‐weight kininogen blocks this pathway by blocking FXII binding to uPAR. uPAR interacts with β1 integrins and this pathway is blocked by mab 6S6. Through mechanisms not completely known, the integrin interacts with endothelial cell growth factor receptor (EGFR). EGFR kinase inhibitors AG1478 and PP3 block this pathway. VEGFR2 also blocks FXII signaling in part, in this pathway. This pathway leads to pERK1/2 and pAktS⁴⁷³ expression. The MEK inhibitor PD98059 and the PI3 kinase inhibitor LY294002 block these phosphoproteins, respectively. Finally, unimpeded this signaling pathway leads to cell proliferation and angiogenesis. Any of the inhibitors enumerated above will block this process. FXII, factor XII; uPAR, urokinase plasminogen activator receptor