Schematic model for uPA/α_Mβ₂/uPAR interactions.

uPAR binds to the GFD of HMW-uPA (A), and this interaction enhances complex formation between uPAR and α_Mβ₂ (B) on the cell surface. In this complex (B), uPAR binds the α_M subunit of α_Mβ₂, via M25 sequence, adjacent to the α_MI domain. When uPA/uPAR is in complex with α_Mβ₂, this facilitates recognition of the kringle domain (KD) and proteolytic domain (LMW-uPA) of HMW-uPA to the α_MI domain of α_Mβ₂ (C). However, α_Mβ₂ is capable of binding HMW-uPA independently from uPAR. (D) Formation of the trimolecular complex (C) enhances adhesion and migration of cells cotransfected with both α_Mβ₂ and uPAR and on cells naturally expressing both receptors, such as neutrophils.