Insights into the regulation of the matriptase-prostasin proteolytic system

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Insights into the regulation of the matriptase-prostasin proteolytic system. / Holt-Danborg, Lasse; Skovbjerg, Signe; Goderum, Kristian W.; Nonboe, Annika W.; Stankevic, Evelina; Frost, Ásdis K.; Vitved, Lars; Jensen, Jan K.; Vogel, Lotte K.

In: The Biochemical journal, Vol. 477, No. 22, 2020, p. 4349-4365.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Holt-Danborg, L, Skovbjerg, S, Goderum, KW, Nonboe, AW, Stankevic, E, Frost, ÁK, Vitved, L, Jensen, JK & Vogel, LK 2020, 'Insights into the regulation of the matriptase-prostasin proteolytic system', The Biochemical journal, vol. 477, no. 22, pp. 4349-4365. https://doi.org/10.1042/BCJ20200630

APA

Holt-Danborg, L., Skovbjerg, S., Goderum, K. W., Nonboe, A. W., Stankevic, E., Frost, Á. K., Vitved, L., Jensen, J. K., & Vogel, L. K. (2020). Insights into the regulation of the matriptase-prostasin proteolytic system. The Biochemical journal, 477(22), 4349-4365. https://doi.org/10.1042/BCJ20200630

Vancouver

Holt-Danborg L, Skovbjerg S, Goderum KW, Nonboe AW, Stankevic E, Frost ÁK et al. Insights into the regulation of the matriptase-prostasin proteolytic system. The Biochemical journal. 2020;477(22):4349-4365. https://doi.org/10.1042/BCJ20200630

Author

Holt-Danborg, Lasse ; Skovbjerg, Signe ; Goderum, Kristian W. ; Nonboe, Annika W. ; Stankevic, Evelina ; Frost, Ásdis K. ; Vitved, Lars ; Jensen, Jan K. ; Vogel, Lotte K. / Insights into the regulation of the matriptase-prostasin proteolytic system. In: The Biochemical journal. 2020 ; Vol. 477, No. 22. pp. 4349-4365.

Bibtex

@article{cf7ffb411a8340b2838a35f71abeb8c5,
title = "Insights into the regulation of the matriptase-prostasin proteolytic system",
abstract = "The membrane-associated prostasin and matriptase belonging to the S1A subfamily of serine proteases, are critical for epithelial development and maintenance. The two proteases are involved in the activation of each other and are both regulated by the protease inhibitors, HAI-1 and HAI-2. The S1A subfamily of serine proteases are generally produced as inactive zymogens requiring a cleavage event to obtain activity. However, contrary to the common case, the zymogen form of matriptase exhibits proteolytic activity, which can be inhibited by HAI-1 and HAI-2, as for the activated counterpart. We provide strong evidence that also prostasin exhibits proteolytic activity in its zymogen form. Furthermore, we show that the activity of zymogen prostasin can be inhibited by HAI-1 and HAI-2. We report that zymogen prostasin is capable of activating zymogen matriptase, but unable to activate its own zymogen form. We propose the existence of an unusual enzyme-enzyme relationship consisting of proteolytically active zymogen forms of both matriptase and prostasin, kept under control by HAI-1 and HAI-2, and located at the pinnacle of an important proteolytic pathway in epithelia. Perturbed balance in this proteolytic system is likely to cause rapid and efficient activation of matriptase by the dual action of zymogen matriptase and zymogen prostasin. Previous studies suggest that the zymogen form of matriptase performs the normal proteolytic functions of the protease, whereas excess matriptase activation likely causes carcinogenesis. HAI-1 and HAI-2 are thus important for the prevention of matriptase activation whether catalysed by zymogen/activated prostasin (this study) or zymogen/activated matriptase (previous studies).",
keywords = "HAI-1, HAI-2, matriptase, prostasin, serine proteases, zymogen activity",
author = "Lasse Holt-Danborg and Signe Skovbjerg and Goderum, {Kristian W.} and Nonboe, {Annika W.} and Evelina Stankevic and Frost, {{\'A}sdis K.} and Lars Vitved and Jensen, {Jan K.} and Vogel, {Lotte K.}",
year = "2020",
doi = "10.1042/BCJ20200630",
language = "English",
volume = "477",
pages = "4349--4365",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "22",

}

RIS

TY - JOUR

T1 - Insights into the regulation of the matriptase-prostasin proteolytic system

AU - Holt-Danborg, Lasse

AU - Skovbjerg, Signe

AU - Goderum, Kristian W.

AU - Nonboe, Annika W.

AU - Stankevic, Evelina

AU - Frost, Ásdis K.

AU - Vitved, Lars

AU - Jensen, Jan K.

AU - Vogel, Lotte K.

PY - 2020

Y1 - 2020

N2 - The membrane-associated prostasin and matriptase belonging to the S1A subfamily of serine proteases, are critical for epithelial development and maintenance. The two proteases are involved in the activation of each other and are both regulated by the protease inhibitors, HAI-1 and HAI-2. The S1A subfamily of serine proteases are generally produced as inactive zymogens requiring a cleavage event to obtain activity. However, contrary to the common case, the zymogen form of matriptase exhibits proteolytic activity, which can be inhibited by HAI-1 and HAI-2, as for the activated counterpart. We provide strong evidence that also prostasin exhibits proteolytic activity in its zymogen form. Furthermore, we show that the activity of zymogen prostasin can be inhibited by HAI-1 and HAI-2. We report that zymogen prostasin is capable of activating zymogen matriptase, but unable to activate its own zymogen form. We propose the existence of an unusual enzyme-enzyme relationship consisting of proteolytically active zymogen forms of both matriptase and prostasin, kept under control by HAI-1 and HAI-2, and located at the pinnacle of an important proteolytic pathway in epithelia. Perturbed balance in this proteolytic system is likely to cause rapid and efficient activation of matriptase by the dual action of zymogen matriptase and zymogen prostasin. Previous studies suggest that the zymogen form of matriptase performs the normal proteolytic functions of the protease, whereas excess matriptase activation likely causes carcinogenesis. HAI-1 and HAI-2 are thus important for the prevention of matriptase activation whether catalysed by zymogen/activated prostasin (this study) or zymogen/activated matriptase (previous studies).

AB - The membrane-associated prostasin and matriptase belonging to the S1A subfamily of serine proteases, are critical for epithelial development and maintenance. The two proteases are involved in the activation of each other and are both regulated by the protease inhibitors, HAI-1 and HAI-2. The S1A subfamily of serine proteases are generally produced as inactive zymogens requiring a cleavage event to obtain activity. However, contrary to the common case, the zymogen form of matriptase exhibits proteolytic activity, which can be inhibited by HAI-1 and HAI-2, as for the activated counterpart. We provide strong evidence that also prostasin exhibits proteolytic activity in its zymogen form. Furthermore, we show that the activity of zymogen prostasin can be inhibited by HAI-1 and HAI-2. We report that zymogen prostasin is capable of activating zymogen matriptase, but unable to activate its own zymogen form. We propose the existence of an unusual enzyme-enzyme relationship consisting of proteolytically active zymogen forms of both matriptase and prostasin, kept under control by HAI-1 and HAI-2, and located at the pinnacle of an important proteolytic pathway in epithelia. Perturbed balance in this proteolytic system is likely to cause rapid and efficient activation of matriptase by the dual action of zymogen matriptase and zymogen prostasin. Previous studies suggest that the zymogen form of matriptase performs the normal proteolytic functions of the protease, whereas excess matriptase activation likely causes carcinogenesis. HAI-1 and HAI-2 are thus important for the prevention of matriptase activation whether catalysed by zymogen/activated prostasin (this study) or zymogen/activated matriptase (previous studies).

KW - HAI-1

KW - HAI-2

KW - matriptase

KW - prostasin

KW - serine proteases

KW - zymogen activity

U2 - 10.1042/BCJ20200630

DO - 10.1042/BCJ20200630

M3 - Journal article

C2 - 33094801

AN - SCOPUS:85096946981

VL - 477

SP - 4349

EP - 4365

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 22

ER -

ID: 252676745