ArticleThe Journal of biological chemistry2012
Characterization of heparin-binding site of tissue transglutaminase: its importance in cell surface targeting, matrix deposition, and cell signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 70 citations in OpenAlex.
- Targeting the Primordial Chaperone to Overcome Acquired Drug Resistance in Cancer: TG2-Mediated Autophagy.Biomolecules & therapeutics · 2026Review
- Discovery of Heparin Mimetic, Potent, and Selective Inhibitors of Human Clotting Factor XIIIa.ACS omega · 2024Article
- The Role of Transglutaminase 2 in Cancer: An Update.International journal of molecular sciences · 2024Review
- Design and Evolution of Enhanced Peptide-Peptide Ligation for Modular Transglutaminase Assembly.Bioconjugate chemistry · 2023Article
- Targeting transglutaminase 2 mediated exostosin glycosyltransferase 1 signaling in liver cancer stem cells with acyclic retinoid.Cell death & disease · 2023Article
- Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation.Scientific reports · 2022Article
- Transglutaminase 2: a novel therapeutic target for idiopathic pulmonary fibrosis using selective small molecule inhibitors.Amino acids · 2021Article
- Factor XIIIa inhibitors as potential novel drugs for venous thromboembolism.European journal of medicinal chemistry · 2020Review
- Design of anti-inflammatory heparan sulfate to protect against acetaminophen-induced acute liver failure.Science translational medicine · 2020Article
- Transglutaminase 2 maintains a colorectal cancer stem phenotype by regulating epithelial-mesenchymal transition.Oncotarget · 2019Article
- Spotlight on the Transglutaminase 2-Heparan Sulfate Interaction.Medical sciences (Basel, Switzerland) · 2019Review
- Biocatalysis by Transglutaminases: A Review of Biotechnological Applications.Micromachines · 2018Review
- Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor.Cell death & disease · 2018Article
- Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction.Journal of the American Society of Nephrology : JASN · 2018Article
- The functional relationship between transglutaminase 2 and transforming growth factor β1 in the regulation of angiogenesis and endothelial-mesenchymal transition.Cell death & disease · 2017Article
- Transglutaminase 2 in human diseases.BioMedicine · 2017Article
- The Soft- and Hard-Heartedness of Cardiac Fibroblasts: Mechanotransduction Signaling Pathways in Fibrosis of the Heart.Journal of clinical medicine · 2017Review
- Tissue transglutaminase induces Epithelial-Mesenchymal-Transition and the acquisition of stem cell like characteristics in colorectal cancer cells.Oncotarget · 2017Article
- Transglutaminase 2 in cartilage homoeostasis: novel links with inflammatory osteoarthritis.Amino acids · 2017Review
- Soluble Syndecan-1: A Novel Biomarker of Small Bowel Mucosal Damage in Children with Celiac Disease.Digestive diseases and sciences · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue transglutaminase (TG2) is a multifunctional Ca(2+)-activated protein cross-linking enzyme secreted into the extracellular matrix (ECM), where it is involved in wound healing and scarring, tissue fibrosis, celiac disease, and metastatic cancer. Extracellular TG2 can also facilitate cell adhesion important in wound healing through a nontransamidating mechanism via its association with fibronectin, heparan sulfates (HS), and integrins. Regulating the mechanism how TG2 is translocated into the ECM therefore provides a strategy for modulating these physiological and pathological functions of the enzyme. Here, through molecular modeling and mutagenesis, we have identified the HS-binding site of TG2 (202)KFLKNAGRDCSRRSSPVYVGR(222). We demonstrate the requirement of this binding site for translocation of TG2 into the ECM through a mechanism involving cell surface shedding of HS. By synthesizing a peptide NPKFLKNAGRDCSRRSS corresponding to the HS-binding site within TG2, we also demonstrate how this mimicking peptide can in isolation compensate for the RGD-induced loss of cell adhesion on fibronectin via binding to syndecan-4, leading to activation of PKCα, pFAK-397, and ERK1/2 and the subsequent formation of focal adhesions and actin cytoskeleton organization. A novel regulatory mechanism for TG2 translocation into the extracellular compartment that depends upon TG2 conformation and the binding of HS is proposed.
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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.