Identification and characterization of a novel rat ov-serpin family member, trespin
| Autor: | Jerry E. Chipuk, Kyung Song, Annalisa Ranieri, LaMonica V. Stewart, David Danielpour |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Models Molecular Arginine Plasmin Molecular Sequence Data Biology Serpin Biochemistry Cell Line Transforming Growth Factor beta1 Transforming Growth Factor beta medicine Animals Humans Amino Acid Sequence Fibrinolysin RNA Messenger Cloning Molecular Molecular Biology Cellular localization Serpins Differential display Chymotrypsin Molecular mass Sequence Homology Amino Acid Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Prostate Cell Biology Trypsin Molecular biology Rats biology.protein medicine.drug |
| Zdroj: | The Journal of biological chemistry. 277(29) |
| ISSN: | 0021-9258 |
| Popis: | Serpins are responsible for regulating a variety of proteolytic processes through a unique irreversible suicide substrate mechanism. To discover novel genes regulated by transforming growth factor-beta1 (TGF-beta 1), we performed differential display reverse transcriptase-PCR analysis of NRP-152 rat prostatic epithelial cells and cloned a novel rat serpin that is transcriptionally down-regulated by TGF-beta and hence named trespin (TGF-beta-repressible serine proteinase inhibitor (trespin). Trespin is a 397-amino acid member of the ov-serpin clade with a calculated molecular mass of 45.2 kDa and 72% amino acid sequence homology to human bomapin; however, trespin exhibits different tissue expression, cellular localization, and proteinase specificity compared with bomapin. Trespin mRNA is expressed in many tissues, including brain, heart, kidney, liver, lung, prostate, skin, spleen, and stomach. FLAG-trespin expressed in HEK293 cells is localized predominantly in the cytoplasm and is not constitutively secreted. The presence of an arginine at the P1 position of trespin's reactive site loop suggests that trespin inhibits trypsin-like proteinases. Accordingly, in vitro transcribed and translated trespin forms detergent-stable and thermostable complexes with plasmin and elastase but not subtilisin A, trypsin, chymotrypsin, thrombin, or papain. Trespin interacts with plasmin at a near 1:1 stoichiometry, and immunopurified mammal-expressed trespin inhibits plasmin in a dose-dependent manner. These data suggest that trespin is a novel and functional member of the rat ov-serpin family. |
| Databáze: | OpenAIRE |
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