ArticleThe Journal of biological chemistry2011
A crucial sequence for transglutaminase type 2 extracellular trafficking in renal tubular epithelial cells lies in its N-terminal beta-sandwich domain.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Randomized Phase 1 Studies Evaluating the Safety, Tolerability, Pharmacokinetics, and Target Occupancy of Zampilimab in Healthy Participants.Clinical pharmacology in drug development · 2026Trial
- Glycomimetic Peptides as Therapeutic Tools.Pharmaceutics · 2023Review
- Resolution of Eczema with Multivalent Peptides.JID innovations : skin science from molecules to population health · 2022Article
- The Discovery and Function of Filaggrin.International journal of molecular sciences · 2022Review
- Urinary levels of pro-fibrotic transglutaminase 2 (TG2) may help predict progression of chronic kidney disease.PloS one · 2022Article
- Spotlight on the Transglutaminase 2-Heparan Sulfate Interaction.Medical sciences (Basel, Switzerland) · 2019Review
- Renal Cell Carcinoma Is Abrogated by p53 Stabilization through Transglutaminase 2 Inhibition.Cancers · 2018Article
- New Insights into Development of Transglutaminase 2 Inhibitors as Pharmaceutical Lead Compounds.Medical sciences (Basel, Switzerland) · 2018Review
- Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction.Journal of the American Society of Nephrology : JASN · 2018Article
- Tissue transglutaminase in astrocytes is enhanced by inflammatory mediators and is involved in the formation of fibronectin fibril-like structures.Journal of neuroinflammation · 2017Article
- Article
- Interplay between transglutaminases and heparan sulphate in progressive renal scarring.Scientific reports · 2016Article
- Urinary myeloid IgA Fc alpha receptor (CD89) and transglutaminase-2 as new biomarkers for active IgA nephropathy and henoch-Schönlein purpura nephritis.BBA clinical · 2016Article
- P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2.Journal of cell science · 2015Article
- Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis.Journal of the American Society of Nephrology : JASN · 2014Article
- Upregulation of transglutaminase and ε (γ-glutamyl)-lysine in the Fisher-Lewis rat model of chronic allograft nephropathy.BioMed research international · 2014Article
- Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer.Oncogene · 2012Article
- Characterization of heparin-binding site of tissue transglutaminase: its importance in cell surface targeting, matrix deposition, and cell signaling.The Journal of biological chemistry · 2012Article
- Cellular functions of tissue transglutaminase.International review of cell and molecular biology · 2012Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transglutaminase type 2 (TG2) catalyzes the formation of an ε-(γ-glutamyl)-lysine isopeptide bond between adjacent peptides or proteins including those of the extracellular matrix (ECM). Elevated extracellular TG2 leads to accelerated ECM deposition and reduced clearance that underlie tissue scarring and fibrosis. The extracellular trafficking of TG2 is crucial to its role in ECM homeostasis; however, the mechanism by which TG2 escapes the cell is unknown as it has no signal leader peptide and therefore cannot be transported classically. Understanding TG2 transport may highlight novel mechanisms to interfere with the extracellular function of TG2 as isoform-specific TG2 inhibitors remain elusive. Mammalian expression vectors were constructed containing domain deletions of TG2. These were transfected into three kidney tubular epithelial cell lines, and TG2 export was assessed to identify critical domains. Point mutation was then used to highlight specific sequences within the domain required for TG2 export. The removal of β-sandwich domain prevented all TG2 export. Mutations of Asp(94) and Asp(97) within the N-terminal β-sandwich domain were identified as crucial for TG2 externalization. These form part of a previously identified fibronectin binding domain ((88)WTATVVDQQDCTLSLQLTT(106)). However, siRNA knockdown of fibronectin failed to affect TG2 export. The sequence (88)WTATVVDQQDCTLSLQLTT(106) within the β-sandwich domain of TG2 is critical to its export in tubular epithelial cell lines. The extracellular trafficking of TG2 is independent of fibronectin.
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