Generation of engineered recombinant hepatocyte growth factor cleaved and activated by Genenase I
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金沢大学がん研究所附属分子標的がん医療研究開発センター
Hepatocyte growth factor (HGF) is biosynthesized as a biologically inactive, single-chain form (pro-HGF). Its activation is associated with cleavage at Arg494-Val495 into a two-chain mature form composed of disulfide-linked α- and β-chains. Because serum is a major source of HGF activator (the predominant serine protease responsible for the processing of pro-HGF), serum-free production of recombinant, two-chain HGF had not been established. In this study, to enable serum-free production of two-chain HGF, we generated engineered human pro-HGFs that can be specifically cleaved and activated by Genenase I. Since Genenase I specifically cleaves the C-terminus of the His-Tyr sequence, which does not exist in human HGF, Arg494 (the C-terminus of the HGF α-chain) was replaced by His-Tyr, Ala-Ala-His-Tyr, Pro-Gly-His-Tyr, or Pro-Gly-Ala-Ala-His-Tyr. Genenase I cleaved engineered pro-HGFs specifically at the replaced amino acid sequences, forming a disulfide-linked two-chain form. The cleavage was most efficient in the case of the Pro-Gly-Ala-Ala-His-Tyr sequence, and cleaved HGFs displayed biological activities identical to those of wild-type HGF. Considering a potential medical application of HGF, the present technique is valuable because it enables the production of recombinant, two-chain HGF entirely without serum and extends the choice of host cells and organisms for recombinant production. © 2007 Elsevier B.V. All rights reserved.
収録刊行物
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- Journal of Biotechnology
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Journal of Biotechnology 133 (4), 478-485, 2008-02-29
Elsevier
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詳細情報 詳細情報について
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- CRID
- 1390576900005963520
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- NII論文ID
- 120000811714
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- NII書誌ID
- AA10458361
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- ISSN
- 01681656
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- Web Site
- http://hdl.handle.net/2297/8955
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- IRDB
- CiNii Articles