Activin A Binds to Perlecan through Its Pro-region That Has Heparin/Heparan Sulfate Binding Activity

Li, Shaoliang; Shimono, Chisei; Norioka, Naoko; Nakano, Itsuko; Okubo, Tetsuo; Yagi, Yoshiko; Hayashi, Maria; Sato, Yuya; Fujisaki, Hitomi; Hattori, Shunji; Sugiura, Nobuo; Kimata, Koji; Sekiguchi, Kiyotoshi

doi:https://doi.org/10.1074/jbc.M110.177865

Activin A Binds to Perlecan through Its Pro-region That Has Heparin/Heparan Sulfate Binding Activity

Li, Shaoliang; Shimono, Chisei; Norioka, Naoko et al.

Journal of Biological Chemistry, 2010, 285(47), 36645-36655

アクセス数:1,012件（2025-10-24 14:10 集計）

固定URL: https://hdl.handle.net/11094/71421

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タイトル	Activin A Binds to Perlecan through Its Pro-region That Has Heparin/Heparan Sulfate Binding Activity
著者	NRID 1000040252720 1000040252720 著者名 Li, Shaoliang
	著者名 Shimono, Chisei
	著者名 Norioka, Naoko
	著者名 Nakano, Itsuko
	著者名 Okubo, Tetsuo
	著者名 Yagi, Yoshiko
	著者名 Hayashi, Maria
	著者名 Sato, Yuya
	著者名 Fujisaki, Hitomi
	著者名 Hattori, Shunji
	NRID 1000090454420 1000090454420 著者名 Sugiura, Nobuo
	NRID 1000010022641 1000010022641 著者名 Kimata, Koji
	NRID 1000050187845 1000050187845 researchmap permalink read0054833 read0054833 Scopus Author ID 7201662709 7201662709 ORCID 0000-0002-6433-1410 0000-0002-6433-1410 著者名 Sekiguchi, Kiyotoshi
内容	This research was originally published in the Journal of Biological Chemistry. Shaoliang Li, Chisei Shimono, Naoko Norioka, Itsuko Nakano, Tetsuo Okubo, Yoshiko Yagi, Maria Hayashi, Yuya Sato, Hitomi Fujisaki, Shunji Hattori, Nobuo Sugiura, Koji Kimata and Kiyotoshi Sekiguchi. Activin A Binds to Perlecan through Its Pro-region That Has Heparin/Heparan Sulfate Binding Activity. J. Biol. Chem. 2010; 285: 36645-36655 © the American Society for Biochemistry and Molecular Biology
抄録	Activin A, a member of the transforming growth factor-β family, plays important roles in hormonal homeostasis and embryogenesis. In this study, we produced recombinant human activin A and examined its abilities to bind to extracellular matrix proteins. Recombinant activin A expressed in 293-F cells was purified as complexes of mature dimeric activin A with its pro-region. Among a panel of extracellular matrix proteins tested, recombinant activin A bound to perlecan and agrin, but not to laminins, nidogens, collagens I and IV, fibronectin, and nephronectin. The binding of recombinant activin A to perlecan was inhibited by heparin and high concentrations of NaCl and abolished by heparitinase treatment of perlecan, suggesting that activin A binds to the heparan sulfate chains of perlecan. In support of this possibility, recombinant activin A was capable of directly binding to heparin and heparan sulfate chains. Site-directed mutagenesis of recombinant activin A revealed that clusters of basic amino acid residues, Lys259-Lys263 and Lys270-Lys272, in the pro-region were required for binding to perlecan. Interestingly, deletion of the peptide segment Lys259-Gly277 containing both basic amino acid clusters from the pro-region did not impair the activity of activin A to stimulate Smad-dependent gene expressions, although it completely ablated the perlecan-binding activity. The binding of activin A to basement membrane heparan sulfate proteoglycans through the basic residues in the pro-region was further confirmed by in situ activin A overlay assays using frozen tissue sections. Taken together, the present results indicate that activin A binds to heparan sulfate proteoglycans through its pro-region and thereby regulates its localization within tissues.
出版者	American Society for Biochemistry and Molecular Biology
収録物名	Journal of Biological Chemistry
巻(号)	285(47)
ページ	36645-36655
刊行年月	2010-11
言語	英語
ハンドルURL	https://hdl.handle.net/11094/71421
eISSN	1083351X
NCID	AA1202441X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1074/jbc.M110.177865
アクセス権	open access
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2010, 285(47), p. 36645-36655
DC.title	Activin A Binds to Perlecan through Its Pro-region That Has Heparin/Heparan Sulfate Binding Activity
DC.creator	Li, Shaoliang
	Shimono, Chisei
	Norioka, Naoko
	Nakano, Itsuko
	Okubo, Tetsuo
	Yagi, Yoshiko
	Hayashi, Maria
	Sato, Yuya
	Fujisaki, Hitomi
	Hattori, Shunji
	Sugiura, Nobuo
	Kimata, Koji
	Sekiguchi, Kiyotoshi
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2010-11
DC.identifier	https://doi.org/10.1074/jbc.M110.177865
DC.description	This research was originally published in the Journal of Biological Chemistry. Shaoliang Li, Chisei Shimono, Naoko Norioka, Itsuko Nakano, Tetsuo Okubo, Yoshiko Yagi, Maria Hayashi, Yuya Sato, Hitomi Fujisaki, Shunji Hattori, Nobuo Sugiura, Koji Kimata and Kiyotoshi Sekiguchi. Activin A Binds to Perlecan through Its Pro-region That Has Heparin/Heparan Sulfate Binding Activity. J. Biol. Chem. 2010; 285: 36645-36655 © the American Society for Biochemistry and Molecular Biology
DCTERMS.abstract	Activin A, a member of the transforming growth factor-β family, plays important roles in hormonal homeostasis and embryogenesis. In this study, we produced recombinant human activin A and examined its abilities to bind to extracellular matrix proteins. Recombinant activin A expressed in 293-F cells was purified as complexes of mature dimeric activin A with its pro-region. Among a panel of extracellular matrix proteins tested, recombinant activin A bound to perlecan and agrin, but not to laminins, nidogens, collagens I and IV, fibronectin, and nephronectin. The binding of recombinant activin A to perlecan was inhibited by heparin and high concentrations of NaCl and abolished by heparitinase treatment of perlecan, suggesting that activin A binds to the heparan sulfate chains of perlecan. In support of this possibility, recombinant activin A was capable of directly binding to heparin and heparan sulfate chains. Site-directed mutagenesis of recombinant activin A revealed that clusters of basic amino acid residues, Lys259-Lys263 and Lys270-Lys272, in the pro-region were required for binding to perlecan. Interestingly, deletion of the peptide segment Lys259-Gly277 containing both basic amino acid clusters from the pro-region did not impair the activity of activin A to stimulate Smad-dependent gene expressions, although it completely ablated the perlecan-binding activity. The binding of activin A to basement membrane heparan sulfate proteoglycans through the basic residues in the pro-region was further confirmed by in situ activin A overlay assays using frozen tissue sections. Taken together, the present results indicate that activin A binds to heparan sulfate proteoglycans through its pro-region and thereby regulates its localization within tissues.
DC.format	71421
citation_title	Activin A Binds to Perlecan through Its Pro-region That Has Heparin/Heparan Sulfate Binding Activity
citation_author	Li, Shaoliang
	Shimono, Chisei
	Norioka, Naoko
	Nakano, Itsuko
	Okubo, Tetsuo
	Yagi, Yoshiko
	Hayashi, Maria
	Sato, Yuya
	Fujisaki, Hitomi
	Hattori, Shunji
	Sugiura, Nobuo
	Kimata, Koji
	Sekiguchi, Kiyotoshi
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	英語
citation_date	2010-11
citation_journal_title	Journal of Biological Chemistry
citation_volume	285
citation_issue	47
citation_firstpage	36645
citation_lastpage	36655
citation_doi	https://doi.org/10.1074/jbc.M110.177865
citation_public_url	https://hdl.handle.net/11094/71421

Activin A Binds to Perlecan through Its Pro-region That Has Heparin/Heparan Sulfate Binding Activity

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