ArticleThe Journal of biological chemistry2014
N-glycosylation is required for matriptase-2 autoactivation and ectodomain shedding.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Positively charged cytoplasmic residues in corin prevent signal peptidase cleavage and endoplasmic reticulum retention.Communications biology · 2025Article
- Inhibition of DPAGT1 suppresses HER2 shedding and trastuzumab resistance in human breast cancer.The Journal of clinical investigation · 2023Article
- Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.International journal of molecular sciences · 2022Review
- TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region.Biological chemistry · 2022Article
- SEC23B Loss-of-Function Suppresses Hepcidin Expression by Impairing Glycosylation Pathway in Human Hepatic Cells.International journal of molecular sciences · 2022Article
- Article
- Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease.The Journal of biological chemistry · 2020Article
- Article
- The multifaceted role of iron in renal health and disease.Nature reviews. Nephrology · 2020Review
- Cell surface-anchored serine proteases in cancer progression and metastasis.Cancer metastasis reviews · 2019Review
- Article
- The catalytic, stem, and transmembrane portions of matriptase-2 are required for suppressing the expression of the iron-regulatory hormone hepcidin.The Journal of biological chemistry · 2019Article
- Conserved function of the matriptase-prostasin proteolytic cascade during epithelial morphogenesis.PLoS genetics · 2019Article
- Article
- Functional analysis of corin protein domains required for PCSK6-mediated activation.The international journal of biochemistry & cell biology · 2018Article
- SheddomeDB: the ectodomain shedding database for membrane-bound shed markers.BMC bioinformatics · 2017Review
- High Hepsin expression predicts poor prognosis in Gastric Cancer.Scientific reports · 2016Article
- Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats.PloS one · 2016Article
- Distinct roles of N-glycosylation at different sites of corin in cell membrane targeting and ectodomain shedding.The Journal of biological chemistry · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matriptase-2 is a hepatic membrane serine protease that regulates iron homeostasis. Defects in matriptase-2 cause iron deficiency anemia. In cells, matriptase-2 is synthesized as a zymogen. To date, how matriptase-2 expression and activation are regulated remains poorly understood. Here we expressed human matriptase-2 in HEK293 and hepatic BEL-7402, SMMC-7721, and QGY-7703 cells. By labeling cell surface proteins and Western analysis, we examined matriptase-2 cell surface expression, zymogen activation, and ectodomain shedding. Our results show that matriptase-2 was activated on the cell surface but not intracellularly. Activated matriptase-2 underwent ectodomain shedding, producing soluble fragments in the conditioned medium. By testing inactive mutants, R576A and S762A, we found that matriptase-2 activation and shedding were mediated by its own catalytic activity and that the one-chain form of matriptase-2 had little activity in ectodomain shedding. We made additional matriptase-2 mutants, N136Q, N184Q, N216Q, N338Q, N433Q, N453Q, and N518Q, in which each of the predicted N-glycosylation sites was mutated. All of these mutants were expressed on the cell surface. However, mutants N216Q, N453Q, and N518Q, but not the other mutants, had impaired zymogen activation and ectodomain shedding. Our results indicate that N-glycans at specific sites are critical for matriptase-2 activation. Together, these data provide new insights into the cell surface expression, zymogen activation, and ectodomain shedding of matriptase-2.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.