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Cleaved high molecular weight kininogen (HKa) enhances the association of human αvβ3 to the complex formed by urokinase and urokinase plasminogen activator receptor (uPAR)
Author(s) -
Lester Caitlin D.,
Pixley Robin,
Bdeir Khalil,
Cines Douglas,
Colman Robert
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a178-d
Subject(s) - urokinase receptor , supar , high molecular weight kininogen , ternary complex , chemistry , integrin , receptor , microbiology and biotechnology , vitronectin , plasmin , biology , biochemistry , kininogen , enzyme , bradykinin
Tauri et al (Throm Haem 2006) previously reported that urokinase plasminogen activator (uPA) binds directly to integrin αvβ3 through its kringle domain independently of uPAR (CD87). Previous studies also showed that HKa binds to domains 2 and 3 of uPAR (Colman, Pixley et al. JCI 1997). Blassi et al (JBC 2005) demonstrated that αvβ3 and uPAR are associated as detected by a pull‐down assay using anti‐αvβ3 antibody. This information led us to postulate that αvβ3, uPAR and its ligand uPA are capable of forming a ternary complex. We also hypothesized that HKa, another uPAR ligand, would modulate complex formation. We examined the uPA/uPAR/integrin/HKa complex associations using surface plasmon resonance. αvβ3, scuPA (single chain uPA) and HKa each separately bound directly to immobilized suPAR (soluble uPAR). αvβ3 bound to suPAR alone with a kapparent of 3.0 ΔRU/sec. αvβ3 bound to the suPAR‐scuPA complex at a comparable rate. HKa bound similarly to immobilized suPAR and to the binary or ternary complex. When HKa is bound to the suPAR‐scuPA complex it increases the kapparent of αvβ3 to the multi‐protein complex 3 fold to 8.8 ΔRU/sec. The formation of the quaternary complex may enhance signaling by one or more of its components. Cellular studies are being performed to further explore the significance of these findings. Supported NIH R01 CA 83121 and T32 HL07777.