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TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region

  • Carly E. Martin , Andrew S. Murray , Jacob R. Mackinder , Kimberley E. Sala-Hamrick , Michael G. Flynn , Joseph G. Lundgren , Fausto A. Varela und Karin List EMAIL logo
Veröffentlicht/Copyright: 8. Juli 2022
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 403 Heft 10

Abstract

TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. Here we characterize a novel post-translational mechanism important for TMPRSS13 function: proteolytic cleavage within the extracellular TMPRSS13 stem region located between the transmembrane domain and the first site of N-linked glycosylation at asparagine (N)-250 in the scavenger receptor cysteine rich (SRCR) domain. Importantly, the catalytic competence of TMPRSS13 is essential for stem region cleavage, suggesting an autonomous mechanism of action. Site-directed mutagenesis of the 10 basic amino acids (four arginine and six lysine residues) in this region abrogated zymogen activation and catalytic activity of TMPRSS13, as well as phosphorylation, cell surface expression, and shedding. Mutation analysis of individual arginine residues identified R223, a residue located between the low-density lipoprotein receptor class A domain and the SRCR domain, as important for stem region cleavage. Mutation of R223 causes a reduction in the aforementioned functional processing steps of TMPRSS13. These data provide further insight into the roles of different post-translational modifications as regulators of the function and localization of TMPRSS13. Additionally, the data suggest the presence of complex interconnected regulatory mechanisms that may serve to ensure the proper levels of cell-surface and pericellular TMPRSS13-mediated proteolysis under homeostatic conditions.

Keywords: cell-surface serine protease; MSPL; TMPRSS13; TTSP; type II transmembrane serine protease; zymogen activation
Corresponding author: Karin List, Department of Pharmacology, Wayne State University, 540 East Canfield, Detroit, MI 48201, USA; and Department of Oncology, Wayne State University, 540 East Canfield, Detroit, MI 48201, USA, E-mail:

Funding source: DeRoy Testamentary Foundation

Funding source: National Cancer Institute 10.13039/100000054

Award Identifier / Grant number: R01CA160565, R01CA160565-04S, R01CA222359, T32-CA009531

Acknowledgments

We thank Drs. Izabela Podgorski and Heather Gibson, Wayne State University, for critically reading the manuscript and providing input.

  1. Author contributions: CEM and KL conceived the idea of the study and planned the experiments. CEM performed the majority of the experiments. ASM, MGF, JGL, KSH, and JRM, and FAV assisted with plasmid construction, cell line maintenance, transfections, and western blot analysis. CEM and KL wrote the manuscript and prepared the figures. All authors contributed to interpretation and discussion of the results and read, edited, and approved the final version.

  2. Research funding: This work was supported by NIH/NCI R01CA160565 grant (K.L.), NIH/NCI R01CA160565-04S grant (K.L., F.A.V.), NIH/NCI R01CA222359 (K.L), NIH Ruth L. Kirschstein National Research Service Award T32-CA009531 (A.S.M. and C.E.M) and The DeRoy Testamentary Foundation (A.S.M. and C.E.M). The Microscopy, Imaging, and Cytometry Resources Core is supported, in part, by NIH Center grants P30 CA22453 to the Karmanos Cancer Institute and R50 CA251068-01 to Dr. Moin, Wayne State University, and the Perinatology Research Branch of the National Institutes of Child Health and Development. We thank Drs. Izabela Podgorski and Heather Gibson, Wayne State University, for critically reading the manuscript and providing input.

  3. Conflict of interest statement: The authors declare that they have no conflicts of interest with the contents of this article.

References

Antalis, T.M., Bugge, T.H., and Wu, Q. (2011). Membrane-anchored serine proteases in health and disease. Prog. Mol. Biol. Transl. Sci. 99: 1–50, https://doi.org/10.1016/b978-0-12-385504-6.00001-4.Suche in Google Scholar PubMed PubMed Central

Antalis, T.M., Buzza, M.S., Hodge, K.M., Hooper, J.D., and Netzel-Arnett, S. (2010). The cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment. Biochem. J. 428: 325–346, https://doi.org/10.1042/bj20100046.Suche in Google Scholar

Bestle, D., Heindl, M.R., Limburg, H., Van Lam van, T., Pilgram, O., Moulton, H., Stein, D.A., Hardes, K., Eickmann, M., Dolnik, O., et al.. (2020). TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci. Alliance 3: e202000786, https://doi.org/10.26508/lsa.202000786.Suche in Google Scholar PubMed PubMed Central

Bugge, T.H., Antalis, T.M., and Wu, Q. (2009). Type II transmembrane serine proteases. J. Biol. Chem. 284: 23177–23181, https://doi.org/10.1074/jbc.r109.021006.Suche in Google Scholar

Chen, M., Chen, L.M., Lin, C.Y., and Chai, K.X. (2010). Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor. Mol. Cell. Biochem. 337: 259–266, https://doi.org/10.1007/s11010-009-0307-y.Suche in Google Scholar PubMed

Cho, E.G., Kim, M.G., Kim, C., Kim, S.R., Seong, I.S., Chung, C., Schwartz, R.H., and Park, D. (2001). N-terminal processing is essential for release of epithin, a mouse type II membrane serine protease. J. Biol. Chem. 276: 44581–44589, https://doi.org/10.1074/jbc.m107059200.Suche in Google Scholar PubMed

Cho, Y., Kim, S.B., Kim, J., Pham, A.V.Q., Yoon, M.J., Park, J.H., Hwang, K.T., Park, D., Kim, M.G., and Kim, C. (2020). Intramembrane proteolysis of an extracellular serine protease, epithin/PRSS14, enables its intracellular nuclear function. BMC Biol. 18: 60, https://doi.org/10.1186/s12915-020-00787-3.Suche in Google Scholar PubMed PubMed Central

Choi, S.Y., Bertram, S., Glowacka, I., Park, Y.W., and Pöhlmann, S. (2009). Type II transmembrane serine proteases in cancer and viral infections. Trends Mol. Med. 15: 303–312, https://doi.org/10.1016/j.molmed.2009.05.003.Suche in Google Scholar PubMed

Duhaime, M.J., Page, K.O., Varela, F.A., Murray, A.S., Silverman, M.E., Zoratti, G.L., and List, K. (2016). Cell surface human airway trypsin-like protease is lost during squamous cell carcinogenesis. J. Cell. Physiol. 231: 1476–1483, https://doi.org/10.1002/jcp.25173.Suche in Google Scholar PubMed PubMed Central

Enns, C.A., Jue, S., and Zhang, A.S. (2020). The ectodomain of matriptase-2 plays an important nonproteolytic role in suppressing hepcidin expression in mice. Blood 136: 989–1001, https://doi.org/10.1182/blood.2020005222.Suche in Google Scholar PubMed PubMed Central

Friis, S., Sales, K.U., Schafer, J.M., Vogel, L.K., Kataoka, H., and Bugge, T.H. (2014). The protease inhibitor HAI-2, but not HAI-1, regulates matriptase activation and shedding through prostasin. J. Biol. Chem. 289: 22319–22332, https://doi.org/10.1074/jbc.M114.574400.Suche in Google Scholar PubMed PubMed Central

Friis, S., Tadeo, D., Le-Gall, S.M., Jürgensen, H.J., Sales, K.U., Camerer, E., and Bugge, T.H. (2017). Matriptase zymogen supports epithelial development, homeostasis and regeneration. BMC Biol. 15: 46, https://doi.org/10.1186/s12915-017-0384-4.Suche in Google Scholar PubMed PubMed Central

Friis, S., Uzzun Sales, K., Godiksen, S., Peters, D.E., Lin, C.Y., Vogel, L.K., and Bugge, T.H. (2013). A matriptase-prostasin reciprocal zymogen activation complex with unique features: prostasin as a non-enzymatic co-factor for matriptase activation. J. Biol. Chem. 288: 19028–19039, https://doi.org/10.1074/jbc.m113.469932.Suche in Google Scholar PubMed PubMed Central

Harbig, A., Mernberger, M., Bittel, L., Pleschka, S., Schughart, K., Steinmetzer, T., Stiewe, T., Nist, A., and Böttcher-Friebertshäuser, E. (2020). Transcriptome profiling and protease inhibition experiments identify proteases that activate H3N2 influenza A and influenza B viruses in murine airway. J. Biol. Chem. 295: 11388–11407, https://doi.org/10.1074/jbc.RA120.012635.Suche in Google Scholar PubMed PubMed Central

Hashimoto, T., Kato, M., Shimomura, T., and Kitamura, N. (2010). TMPRSS13, a type II transmembrane serine protease, is inhibited by hepatocyte growth factor activator inhibitor type 1 and activates pro-hepatocyte growth factor. FEBS J. 277: 4888–4900, https://doi.org/10.1111/j.1742-4658.2010.07894.x.Suche in Google Scholar PubMed

Hoffmann, M., Hofmann-Winkler, H., Smith, J.C., Krüger, N., Arora, P., Sørensen, L.K., Søgaard, O.S., Hasselstrøm, J.B., Winkler, M., Hempel, T., et al.. (2021). Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity. EBioMedicine 65: 103255, https://doi.org/10.1016/j.ebiom.2021.103255.Suche in Google Scholar PubMed PubMed Central

Hooper, J.D., Clements, J.A., Quigley, J.P., and Antalis, T.M. (2001). Type II transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes. J. Biol. Chem. 276: 857–860, https://doi.org/10.1074/jbc.r000020200.Suche in Google Scholar PubMed

Jiang, J., Wu, S., Wang, W., Chen, S., Peng, J., Zhang, X., and Wu, Q. (2011). Ectodomain shedding and autocleavage of the cardiac membrane protease corin. J. Biol. Chem. 286: 10066–10072, https://doi.org/10.1074/jbc.m110.185082.Suche in Google Scholar PubMed PubMed Central

Jiang, J., Yang, J., Feng, P., Zuo, B., Dong, N., Wu, Q., and He, Y. (2014). N-glycosylation is required for matriptase-2 autoactivation and ectodomain shedding. J. Biol. Chem. 289: 19500–19507, https://doi.org/10.1074/jbc.m114.555110.Suche in Google Scholar PubMed PubMed Central

Kido, H. and Okumura, Y. (2008). MSPL/TMPRSS13. Front. Biosci. 13: 754–758, https://doi.org/10.2741/2717.Suche in Google Scholar PubMed

Kido, H., Okumura, Y., Takahashi, E., Pan, H.Y., Wang, S., Chida, J., Le, T.Q., and Yano, M. (2008). Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses. J. Mol. Genet. Med. 3: 167–175.10.4172/1747-0862.1000029Suche in Google Scholar

Kim, D.R., Sharmin, S., Inoue, M., and Kido, H. (2001). Cloning and expression of novel mosaic serine proteases with and without a transmembrane domain from human lung. Biochim. Biophys. Acta 1518: 204–209, https://doi.org/10.1016/s0167-4781(01)00184-1.Suche in Google Scholar

Kishimoto, M., Uemura, K., Sanaki, T., Sato, A., Hall, W.W., Kariwa, H., Orba, Y., Sawa, H., and Sasaki, M. (2021). TMPRSS11D and TMPRSS13 activate the SARS-CoV-2 spike protein. Viruses 13: 384, https://doi.org/10.3390/v13030384.Suche in Google Scholar PubMed PubMed Central

Lanchec, E., Désilets, A., Béliveau, F., Flamier, A., Mahmoud, S., Bernier, G., Gris, D., Leduc, R., and Lavoie, C. (2017). The type II transmembrane serine protease matriptase cleaves the amyloid precursor protein and reduces its processing to β-amyloid peptide. J. Biol. Chem. 292: 20669–20682, https://doi.org/10.1074/jbc.m117.792911.Suche in Google Scholar PubMed PubMed Central

Laporte, M., Raeymaekers, V., Van Berwaer, R., Vandeput, J., Marchand-Casas, I., Thibaut, H.J., Van Looveren, D., Martens, K., Hoffmann, M., Maes, P., et al.. (2021). The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways. PLoS Pathog. 17: e1009500, https://doi.org/10.1371/journal.ppat.1009500.Suche in Google Scholar PubMed PubMed Central

Larsen, B.R., Steffensen, S.D., Nielsen, N.V., Friis, S., Godiksen, S., Bornholdt, J., Soendergaard, C., Nonboe, A.W., Andersen, M.N., Poulsen, S.S., et al.. (2013). Hepatocyte growth factor activator inhibitor-2 prevents shedding of matriptase. Exp. Cell Res. 319: 918–929, https://doi.org/10.1016/j.yexcr.2013.01.008.Suche in Google Scholar PubMed PubMed Central

Lin, C.Y., Tseng, I.C., Chou, F.P., Su, S.F., Chen, Y.W., Johnson, M.D., and Dickson, R.B. (2008). Zymogen activation, inhibition, and ectodomain shedding of matriptase. Front. Biosci. 13: 621–635, https://doi.org/10.2741/2707.Suche in Google Scholar PubMed

Madsen, D.H., Szabo, R., Molinolo, A.A., and Bugge, T.H. (2014). TMPRSS13 deficiency impairs stratum corneum formation and epidermal barrier acquisition. Biochem. J. 461: 487–495, https://doi.org/10.1042/bj20140337.Suche in Google Scholar

Mao, P., Wortham, A.M., Enns, C.A., and Zhang, A.S. (2019). The catalytic, stem, and transmembrane portions of matriptase-2 are required for suppressing the expression of the iron-regulatory hormone hepcidin. J. Biol. Chem. 294: 2060–2073, https://doi.org/10.1074/jbc.RA118.006468.Suche in Google Scholar PubMed PubMed Central

Martin, C.E. and List, K. (2019). Cell surface-anchored serine proteases in cancer progression and metastasis. Cancer Metastasis Rev. 38: 357–387, https://doi.org/10.1007/s10555-019-09811-7.Suche in Google Scholar PubMed PubMed Central

Martin, C.E., Murray, A.S., Sala-Hamrick, K.E., Mackinder, J.R., Harrison, E.C., Lundgren, J.G., Varela, F.A., and List, K. (2021). Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization. J. Biol. Chem. 297: 101227, https://doi.org/10.1016/j.jbc.2021.101227.Suche in Google Scholar PubMed PubMed Central

Murray, A.S., Hyland, T.E., Sala-Hamrick, K.E., Mackinder, J.R., Martin, C.E., Tanabe, L.M., Varela, F.A., and List, K. (2020). The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy. Oncogene 39: 6421–6436, https://doi.org/10.1038/s41388-020-01436-3.Suche in Google Scholar PubMed PubMed Central

Murray, A.S., Varela, F.A., Hyland, T.E., Schoenbeck, A.J., White, J.M., Tanabe, L.M., Todi, S.V., and List, K. (2017). Phosphorylation of the type II transmembrane serine protease, TMPRSS13, in hepatocyte growth factor activator inhibitor-1 and -2-mediated cell-surface localization. J. Biol. Chem. 292: 14867–14884, https://doi.org/10.1074/jbc.m117.775999.Suche in Google Scholar

Murray, A.S., Varela, F.A., and List, K. (2016). Type II transmembrane serine proteases as potential targets for cancer therapy. Biol. Chem. 397: 815–826, https://doi.org/10.1515/hsz-2016-0131.Suche in Google Scholar PubMed PubMed Central

Netzel-Arnett, S., Hooper, J.D., Szabo, R., Madison, E.L., Quigley, J.P., Bugge, T.H., and Antalis, T.M. (2003). Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Rev. 22: 237–258, https://doi.org/10.1023/a:1023003616848.10.1023/A:1023003616848Suche in Google Scholar

Okumura, Y., Takahashi, E., Yano, M., Ohuchi, M., Daidoji, T., Nakaya, T., Böttcher, E., Garten, W., Klenk, H.D., and Kido, H. (2010). Novel type II transmembrane serine proteases, MSPL and TMPRSS13, Proteolytically activate membrane fusion activity of the hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication. J. Virol. 84: 5089–5096, https://doi.org/10.1128/jvi.02605-09.Suche in Google Scholar PubMed PubMed Central

Schneider, C.A., Rasband, W.S., and Eliceiri, K.W. (2012). NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9: 671–675, https://doi.org/10.1038/nmeth.2089.Suche in Google Scholar PubMed PubMed Central

Silvestri, L., Pagani, A., Nai, A., De Domenico, I., Kaplan, J., and Camaschella, C. (2008). The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metabol. 8: 502–511, https://doi.org/10.1016/j.cmet.2008.09.012.Suche in Google Scholar PubMed PubMed Central

Skovbjerg, S., Holt-Danborg, L., Nonboe, A.W., Hong, Z., Frost, Á., Schar, C.R., Thomas, C.C., Vitved, L., Jensen, J.K., and Vogel, L.K. (2020). Inhibition of an active zymogen protease: the zymogen form of matriptase is regulated by HAI-1 and HAI-2. Biochem. J. 477: 1779–1794, https://doi.org/10.1042/bcj20200182.Suche in Google Scholar PubMed

Stirnberg, M., Maurer, E., Horstmeyer, A., Kolp, S., Frank, S., Bald, T., Arenz, K., Janzer, A., Prager, K., Wunderlich, P., et al.. (2010). Proteolytic processing of the serine protease matriptase-2: identification of the cleavage sites required for its autocatalytic release from the cell surface. Biochem. J. 430: 87–95, https://doi.org/10.1042/bj20091565.Suche in Google Scholar PubMed

Szabo, R. and Bugge, T.H. (2011). Membrane-anchored serine proteases in vertebrate cell and developmental biology. Annu. Rev. Cell Dev. Biol. 27: 213–235, https://doi.org/10.1146/annurev-cellbio-092910-154247.Suche in Google Scholar PubMed PubMed Central

Szabo, R. and Bugge, T.H. (2020). Membrane-anchored serine proteases as regulators of epithelial function. Biochem. Soc. Trans. 48: 517–528, https://doi.org/10.1042/bst20190675.Suche in Google Scholar

Tamberg, T., Hong, Z., De Schepper, D., Skovbjerg, S., Dupont, D.M., Vitved, L., Schar, C.R., Skjoedt, K., Vogel, L.K., and Jensen, J.K. (2019). Blocking the proteolytic activity of zymogen matriptase with antibody-based inhibitors. J. Biol. Chem. 294: 314–326, https://doi.org/10.1074/jbc.ra118.004126.Suche in Google Scholar PubMed PubMed Central

Tanabe, L.M. and List, K. (2017). The role of type II transmembrane serine protease-mediated signaling in cancer. FEBS J. 284: 1421–1436, https://doi.org/10.1111/febs.13971.Suche in Google Scholar PubMed PubMed Central

Tang, X., Mahajan, S.S., Nguyen, L.T., Beliveau, F., Leduc, R., Simon, J.A., and Vasioukhin, V. (2014). Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis. Oncotarget 5: 1352–1362, https://doi.org/10.18632/oncotarget.1817.Suche in Google Scholar PubMed PubMed Central

Tseng, C.-C., Jia, B., Barndt, R., Gu, Y., Chen, C.-Y., Tseng, I.C., Su, S.-F., Wang, J.-K., Johnson, M.D., and Lin, C.-Y. (2017). Matriptase shedding is closely coupled with matriptase zymogen activation and requires de novo proteolytic cleavage likely involving its own activity. PLoS One 12: e0183507, https://doi.org/10.1371/journal.pone.0183507.Suche in Google Scholar PubMed PubMed Central

Varela, F.A., Foust, V.L., Hyland, T.E., Sala-Hamrick, K.E., Mackinder, J.R., Martin, C.E., Murray, A.S., Todi, S.V., and List, K. (2020). TMPRSS13 promotes cell survival, invasion, and resistance to drug-induced apoptosis in colorectal cancer. Sci. Rep. 10: 13896, https://doi.org/10.1038/s41598-020-70636-4.Suche in Google Scholar PubMed PubMed Central

Wang, L., Zhang, C., Sun, S., Chen, Y., Hu, Y., Wang, H., Liu, M., Dong, N., and Wu, Q. (2019). Autoactivation and calpain-1-mediated shedding of hepsin in human hepatoma cells. Biochem. J. 476: 2355–2369, https://doi.org/10.1042/bcj20190375.Suche in Google Scholar

Webb, S.L., Sanders, A.J., Mason, M.D., and Jiang, W.G. (2011). Type II transmembrane serine protease (TTSP) deregulation in cancer. Front. Biosci. (Landmark Ed.) 16: 539–552, https://doi.org/10.2741/3704.Suche in Google Scholar PubMed

Zhang, C., Zhang, Y., Zhang, S., Wang, Z., Sun, S., Liu, M., Chen, Y., Dong, N., and Wu, Q. (2020). Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease. J. Biol. Chem. 295: 12686–12696, https://doi.org/10.1074/jbc.ra120.014525.Suche in Google Scholar

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2022-0129).

Received: 2022-02-28
Accepted: 2022-05-24
Published Online: 2022-07-08
Published in Print: 2022-09-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Research Articles/Short Communications
  3. Cell Biology and Signaling
  4. Diselenide-derivative of 3-pyridinol targets redox enzymes leading to cell cycle deregulation and apoptosis in A549 cells
  5. NF90/NFAR (nuclear factors associated with dsRNA) – a new methylation substrate of the PRMT5-WD45-RioK1 complex
  6. PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1
  7. Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways
  8. LncRNA-p21 suppresses cell proliferation and induces apoptosis in gastric cancer by sponging miR-514b-3p and up-regulating ARHGEF9 expression
  9. L-theanine induces skeletal muscle fiber type transformation by activation of prox1/CaN signaling pathway in C2C12 myotubes
  10. Proteolysis
  11. TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region
https://doi.org/10.1515/hsz-2022-0129
Schlagwörter für diesen Artikel
cell-surface serine protease; MSPL; TMPRSS13; TTSP; type II transmembrane serine protease; zymogen activation

Artikel in diesem Heft

  1. Frontmatter
  2. Research Articles/Short Communications
  3. Cell Biology and Signaling
  4. Diselenide-derivative of 3-pyridinol targets redox enzymes leading to cell cycle deregulation and apoptosis in A549 cells
  5. NF90/NFAR (nuclear factors associated with dsRNA) – a new methylation substrate of the PRMT5-WD45-RioK1 complex
  6. PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1
  7. Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways
  8. LncRNA-p21 suppresses cell proliferation and induces apoptosis in gastric cancer by sponging miR-514b-3p and up-regulating ARHGEF9 expression
  9. L-theanine induces skeletal muscle fiber type transformation by activation of prox1/CaN signaling pathway in C2C12 myotubes
  10. Proteolysis
  11. TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region
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