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Originally published In Press as doi:10.1074/jbc.M002290200 on July 10, 2000

J. Biol. Chem., Vol. 275, Issue 37, 28625-28633, September 15, 2000
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Binding of the NG2 Proteoglycan to Kringle Domains Modulates the Functional Properties of Angiostatin and Plasmin(ogen)*

Lothar GoretzkiDagger , Christian R. Lombardo, and William B. Stallcup§

From the The Burnham Institute, La Jolla Cancer Research Center, La Jolla, California 92037

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.


* This work was supported by National Institutes of Health Grants RO1 NS21990 and RO1 AR44400 (to W. B. S.) and T32 CA09579 (to L. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Current address: Chemicon International, Inc., 28835 Single Oak Dr., Temecula, CA 92590.

§ To whom correspondence should be addressed: The Burnham Inst., La Jolla Cancer Research Center, 10901 North Torrey Pines Rd., La  Jolla, CA 92037. Tel.: 858-646-3100 (ext. 3220); Fax: 858-646-3197; E-mail: stallcup@burnham.org.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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