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Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization

TMPRSS13, a member of the type II transmembrane serine protease (TTSP) family, harbors four N-linked glycosylation sites in its extracellular domain. Two of the glycosylated residues are located in the scavenger receptor cysteine-rich (SRCR) protein domain, while the remaining two sites are in the c...

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Autores principales: Martin, Carly E., Murray, Andrew S., Sala-Hamrick, Kimberley E., Mackinder, Jacob R., Harrison, Evan C., Lundgren, Joseph G., Varela, Fausto A., List, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503615/
https://www.ncbi.nlm.nih.gov/pubmed/34562451
http://dx.doi.org/10.1016/j.jbc.2021.101227
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author Martin, Carly E.
Murray, Andrew S.
Sala-Hamrick, Kimberley E.
Mackinder, Jacob R.
Harrison, Evan C.
Lundgren, Joseph G.
Varela, Fausto A.
List, Karin
author_facet Martin, Carly E.
Murray, Andrew S.
Sala-Hamrick, Kimberley E.
Mackinder, Jacob R.
Harrison, Evan C.
Lundgren, Joseph G.
Varela, Fausto A.
List, Karin
author_sort Martin, Carly E.
collection PubMed
description TMPRSS13, a member of the type II transmembrane serine protease (TTSP) family, harbors four N-linked glycosylation sites in its extracellular domain. Two of the glycosylated residues are located in the scavenger receptor cysteine-rich (SRCR) protein domain, while the remaining two sites are in the catalytic serine protease (SP) domain. In this study, we examined the role of N-linked glycosylation in the proteolytic activity, autoactivation, and cellular localization of TMPRSS13. Individual and combinatory site-directed mutagenesis of the glycosylated asparagine residues indicated that glycosylation of the SP domain is critical for TMPRSS13 autoactivation and catalytic activity toward one of its protein substrates, the prostasin zymogen. Additionally, SP domain glycosylation-deficient TMPRSS13 displayed impaired trafficking of TMPRSS13 to the cell surface, which correlated with increased retention in the endoplasmic reticulum. Importantly, we showed that N-linked glycosylation was a critical determinant for subsequent phosphorylation of endogenous TMPRSS13. Taken together, we conclude that glycosylation plays an important role in regulating TMPRSS13 activation and activity, phosphorylation, and cell surface localization.
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spelling pubmed-85036152021-10-18 Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization Martin, Carly E. Murray, Andrew S. Sala-Hamrick, Kimberley E. Mackinder, Jacob R. Harrison, Evan C. Lundgren, Joseph G. Varela, Fausto A. List, Karin J Biol Chem Research Article TMPRSS13, a member of the type II transmembrane serine protease (TTSP) family, harbors four N-linked glycosylation sites in its extracellular domain. Two of the glycosylated residues are located in the scavenger receptor cysteine-rich (SRCR) protein domain, while the remaining two sites are in the catalytic serine protease (SP) domain. In this study, we examined the role of N-linked glycosylation in the proteolytic activity, autoactivation, and cellular localization of TMPRSS13. Individual and combinatory site-directed mutagenesis of the glycosylated asparagine residues indicated that glycosylation of the SP domain is critical for TMPRSS13 autoactivation and catalytic activity toward one of its protein substrates, the prostasin zymogen. Additionally, SP domain glycosylation-deficient TMPRSS13 displayed impaired trafficking of TMPRSS13 to the cell surface, which correlated with increased retention in the endoplasmic reticulum. Importantly, we showed that N-linked glycosylation was a critical determinant for subsequent phosphorylation of endogenous TMPRSS13. Taken together, we conclude that glycosylation plays an important role in regulating TMPRSS13 activation and activity, phosphorylation, and cell surface localization. American Society for Biochemistry and Molecular Biology 2021-09-22 /pmc/articles/PMC8503615/ /pubmed/34562451 http://dx.doi.org/10.1016/j.jbc.2021.101227 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Martin, Carly E.
Murray, Andrew S.
Sala-Hamrick, Kimberley E.
Mackinder, Jacob R.
Harrison, Evan C.
Lundgren, Joseph G.
Varela, Fausto A.
List, Karin
Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization
title Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization
title_full Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization
title_fullStr Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization
title_full_unstemmed Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization
title_short Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization
title_sort posttranslational modifications of serine protease tmprss13 regulate zymogen activation, proteolytic activity, and cell surface localization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503615/
https://www.ncbi.nlm.nih.gov/pubmed/34562451
http://dx.doi.org/10.1016/j.jbc.2021.101227
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