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