Figure 2

Tissue factor-FVIIa-PAR2 complex-related intracellular signaling. Binding of activated factor VII (FVIIa) leads to proteoyltic cleavage of protease-activated receptor-2 (PAR-2), resulting in loss of negative regulatory control of PAR-2-mediated signaling through phosphorylation of TF cytoplasmic domain. This leads to activation of mitogen-activated protein kinase (MAPK) pathways and PI3K/Akt/mTOR activation. These pathways lead to subsequent gene transcription and result in the production of various mediators like vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), colony-stimulating factor-1 (CSF-1), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI), and survivin. These mediators then play an important role in angiogenesis, tumor growth, invasion, and increased survival. mTOR, mammalian target of ripamycin; P, phosphate; PI3K, phosphatidylinositol 3 kinase.