Roles of CUB and LDL Receptor Class A Domain Repeats of a Transmembrane Serine Protease Matriptase in Its Zymogen Activation

Overview

Journal J Biochem

Publisher Oxford University Press

Specialty Biochemistry

Date 2012 Oct 6

PMID 23038671

Citations 5

Authors

Kuniyo Inouye

Marie Tomoishi

Makoto Yasumoto

Yuka Miyake

Kenji Kojima

Satoshi Tsuzuki

Tohru Fushiki

Affiliations

Soon will be listed here.

Abstract

Matriptase is a type II transmembrane serine protease containing two complement proteases C1r/C1s-urchin embryonic growth factor-bone morphogenetic protein domains (CUB repeat) and four low-density lipoprotein receptor class A domains (LDLRA repeat). The single-chain zymogen of matriptase has been found to exhibit substantial protease activity, possibly causing its own activation (i.e. conversion to a disulfide-linked two-chain fully active form), although the activation seems to be mediated predominantly by two-chain molecules. Our aim was to assess the roles of CUB and LDLRA repeats in zymogen activation. Transient expression studies of soluble truncated constructs of recombinant matriptase in COS-1 cells showed that the CUB repeat had an inhibitory effect on zymogen activation, possibly because it facilitated the interaction of two-chain molecules with a matriptase inhibitor, hepatocyte growth factor activator inhibitor type-1. By contrast, the LDLRA repeat had a promoting effect on zymogen activation. The effect of the LDLRA repeat seems to reflect its ability to increase zymogen activity. The proteolytic activities were higher in pseudozymogen forms of recombinant matriptase containing the LDLRA repeat than in a pseudozymogen without the repeat. Our findings provide new insights into the roles of these non-catalytic domains in the generation of active matriptase.

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References

Fass D, Blacklow S, Kim P, Berger J . Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module. Nature. 1997; 388(6643):691-3. DOI: 10.1038/41798. View

Bork P, Beckmann G . The CUB domain. A widespread module in developmentally regulated proteins. J Mol Biol. 1993; 231(2):539-45. DOI: 10.1006/jmbi.1993.1305. View

Tsuzuki S, Murai N, Miyake Y, Inouye K, Hirayasu H, Iwanaga T . Evidence for the occurrence of membrane-type serine protease 1/matriptase on the basolateral sides of enterocytes. Biochem J. 2005; 388(Pt 2):679-87. PMC: 1138976. DOI: 10.1042/BJ20041639. View

Takeuchi T, Shuman M, Craik C . Reverse biochemistry: use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue. Proc Natl Acad Sci U S A. 1999; 96(20):11054-61. PMC: 34240. DOI: 10.1073/pnas.96.20.11054. View

Inouye K, Tsuzuki S, Yasumoto M, Kojima K, Mochida S, Fushiki T . Identification of the matriptase second CUB domain as the secondary site for interaction with hepatocyte growth factor activator inhibitor type-1. J Biol Chem. 2010; 285(43):33394-33403. PMC: 2963394. DOI: 10.1074/jbc.M110.115816. View

Oberst M, Williams C, Dickson R, Johnson M, Lin C . The activation of matriptase requires its noncatalytic domains, serine protease domain, and its cognate inhibitor. J Biol Chem. 2003; 278(29):26773-9. DOI: 10.1074/jbc.M304282200. View

Bugge T, List K, Szabo R . Matriptase-dependent cell surface proteolysis in epithelial development and pathogenesis. Front Biosci. 2007; 12:5060-70. DOI: 10.2741/2448. View

Miyake Y, Yasumoto M, Tsuzuki S, Fushiki T, Inouye K . Activation of a membrane-bound serine protease matriptase on the cell surface. J Biochem. 2009; 146(2):273-82. DOI: 10.1093/jb/mvp066. View

Moestrup S . The alpha 2-macroglobulin receptor and epithelial glycoprotein-330: two giant receptors mediating endocytosis of multiple ligands. Biochim Biophys Acta. 1994; 1197(2):197-213. DOI: 10.1016/0304-4157(94)90005-1. View

10.

Satomi S, Yamasaki Y, Tsuzuki S, Hitomi Y, Iwanaga T, Fushiki T . A role for membrane-type serine protease (MT-SP1) in intestinal epithelial turnover. Biochem Biophys Res Commun. 2001; 287(4):995-1002. DOI: 10.1006/bbrc.2001.5686. View

11.

Wang J, Lee M, Tseng I, Chou F, Chen Y, Fulton A . Polarized epithelial cells secrete matriptase as a consequence of zymogen activation and HAI-1-mediated inhibition. Am J Physiol Cell Physiol. 2009; 297(2):C459-70. PMC: 2724094. DOI: 10.1152/ajpcell.00201.2009. View

12.

List K, Haudenschild C, Szabo R, Chen W, Wahl S, Swaim W . Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis. Oncogene. 2002; 21(23):3765-79. DOI: 10.1038/sj.onc.1205502. View

13.

List K, Kosa P, Szabo R, Bey A, Wang C, Molinolo A . Epithelial integrity is maintained by a matriptase-dependent proteolytic pathway. Am J Pathol. 2009; 175(4):1453-63. PMC: 2751542. DOI: 10.2353/ajpath.2009.090240. View

14.

Lee M, Tseng I, Wang Y, Kiyomiya K, Johnson M, Dickson R . Autoactivation of matriptase in vitro: requirement for biomembrane and LDL receptor domain. Am J Physiol Cell Physiol. 2007; 293(1):C95-105. DOI: 10.1152/ajpcell.00611.2006. View

15.

Desilets A, Beliveau F, Vandal G, McDuff F, Lavigne P, Leduc R . Mutation G827R in matriptase causing autosomal recessive ichthyosis with hypotrichosis yields an inactive protease. J Biol Chem. 2008; 283(16):10535-42. PMC: 2447636. DOI: 10.1074/jbc.M707012200. View

16.

WILLIAMS E, Krishnaswamy S, Mann K . Zymogen/enzyme discrimination using peptide chloromethyl ketones. J Biol Chem. 1989; 264(13):7536-45. View

17.

Takeuchi T, Harris J, Huang W, Yan K, Coughlin S, Craik C . Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates. J Biol Chem. 2000; 275(34):26333-42. DOI: 10.1074/jbc.M002941200. View

18.

Kim M, Chen C, Lyu M, Cho E, Park D, Kozak C . Cloning and chromosomal mapping of a gene isolated from thymic stromal cells encoding a new mouse type II membrane serine protease, epithin, containing four LDL receptor modules and two CUB domains. Immunogenetics. 1999; 49(5):420-8. DOI: 10.1007/s002510050515. View

19.

List K, Szabo R, Molinolo A, Nielsen B, Bugge T . Delineation of matriptase protein expression by enzymatic gene trapping suggests diverging roles in barrier function, hair formation, and squamous cell carcinogenesis. Am J Pathol. 2006; 168(5):1513-25. PMC: 1606590. DOI: 10.2353/ajpath.2006.051071. View

20.

Lee S, Dickson R, Lin C . Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. J Biol Chem. 2000; 275(47):36720-5. DOI: 10.1074/jbc.M007802200. View