Figure 10

A simplified schematic depiction of the role of uPAR in angiogenesis: The uPAR/Pro-uPA interaction leads to the generation of active uPA on the cell surface. This complex binds to vitronectin in the extracellular matrix, allowing interaction with its transmembrane partners, the α/β integrins. This leads to a cascade of activation events resulting in tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin molecules. Through recruitment of other adaptor molecules, such as Src and p130Cas-CRK complex (not shown), Rac is activated. Activated Rac then induces actin filament assembly leading to membrane protrusion and motility. Formation of focal adhesion complexes enables cellular adhesion and migration. The uPA/uPAR complex also generates the serine protease, plasmin that degrades the extracellular matrix (ECM) thereby stimulating conditions for migration and proliferation. The transmembrane partnership between uPA/uPAR and α/β integrins also activates mitogen activated kinase signaling molecules, MEK and ERK1/2, as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling axis. Thus uPAR-dependent multiple signaling events regulates cellular adhesion, proliferation, and migration, events associated with angiogenesis.