Binding of the NG2 proteoglycan to kringle domains modulates the functional properties of angiostatin and plasmin(ogen).
Interactions of the developmentally regulated chondroitin sulfate proteoglycan NG2 with human plasminogen and kringle domain-containing plasminogen fragments have been analyzed by solid-phase immunoassays and by surface plasmon resonance. In immunoassays, the core protein of NG2 binds specifically and saturably to plasminogen, which consists of five kringle domains and a serine protease domain, and to angiostatin, which contains plasminogen kringle domains 1-3. Apparent dissociation constants for these interactions range from 12 to 75 nm. Additional evidence for NG2 interaction with kringle domains comes from its binding to plasminogen kringle domain 4 and to miniplasminogen (kringle domain 5 plus the protease domain) with apparent dissociation constants in the 18-71 nm range. Inhibition of plasminogen and angiostatin binding to NG2 by 6-aminohexanoic acid suggests that lysine binding sites are involved in kringle interaction with NG2. The interaction of NG2 with plasminogen and angiostatin has very interesting functional consequences. 1) Soluble NG2 significantly enhances the activation of plasminogen by urokinase type plasminogen activator. 2) The antagonistic effect of angiostatin on endothelial cell proliferation is inhibited by soluble NG2. Both of these effects of NG2 should make the proteoglycan a positive regulator of the cell migration and proliferation required for angiogenesis.
Goretzki
L
L
The Burnham Institute, La Jolla Cancer Research Center, La Jolla, California 92037, USA.
Lombardo
C R
CR
Stallcup
W B
WB
D043168:Angiostatins; D000818:Animals; D000941:Antigens / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D018082:Kringles; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000502:physiology*; D010958:Plasminogen / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology; D000099216:Chondroitin Sulfate Proteoglycan 4
D043168:Angiostatins; D000941:Antigens; D010446:Peptide Fragments; D010958:Plasminogen; D011509:Proteoglycans; D014568:Urokinase-Type Plasminogen Activator; D000099216:Chondroitin Sulfate Proteoglycan 4