ArticleMolecular biology of the cell2006
Cell surface transglutaminase promotes RhoA activation via integrin clustering and suppression of the Src-p190RhoGAP signaling pathway.
Article in Molecular biology of the cell, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 117 citations in OpenAlex.
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- Critical Role for Transglutaminase 2 in Scleroderma Skin Fibrosis and in the Development of Dermal Sclerosis in a Mouse Model of Scleroderma.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Mesenchymal Transglutaminase 2 Activates Epithelial ADAM17: Link to G-Protein-Coupled Receptor 56 (ADGRG1) Signalling.International journal of molecular sciences · 2024Article
- Shaping Oncogenic Microenvironments: Contribution of Fibronectin.Frontiers in cell and developmental biology · 2024Review
- Vascular mechanotransduction.Physiological reviews · 2023Review
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- Loss of transglutaminase 2 sensitizes for diet-induced obesity-related inflammation and insulin resistance due to enhanced macrophage c-Src signaling.Cell death & disease · 2019Article
- Small Molecules Target the Interaction between Tissue Transglutaminase and Fibronectin.Molecular cancer therapeutics · 2019Article
- Transglutaminase 2: The Maestro of the Oncogenic Mediators in Renal Cell Carcinoma.Medical sciences (Basel, Switzerland) · 2019Review
- The Role of Tissue Transglutaminase in Cancer Cell Initiation, Survival and Progression.Medical sciences (Basel, Switzerland) · 2019Review
- Low Density Receptor-Related Protein 1 Interactions With the Extracellular Matrix: More Than Meets the Eye.Frontiers in cell and developmental biology · 2019Review
- Transglutaminase activity regulates differentiation, migration and fusion of osteoclasts via affecting actin dynamics.Journal of cellular physiology · 2018Article
- Mechanistic role of transglutaminase-2 in focal adhesions.Scientific reports · 2018Article
- Review
- Tissue transglutaminase expression is necessary for adhesion, metastatic potential and cancer stemness of renal cell carcinoma.Cell adhesion & migration · 2018Article
- Transglutaminase 2 in human diseases.BioMedicine · 2017Article
- Lipopolysaccharide and Curcumin Co-Stimulation Potentiates Olfactory Ensheathing Cell Phagocytosis Via Enhancing Their Activation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Article
- Is monocyte- and macrophage-derived tissue transglutaminase involved in inflammatory processes?Amino acids · 2017Review
- Tissue transglutaminase-2 promotes gastric cancer progression via the ERK1/2 pathway.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Tissue transglutaminase (tTG) is a multifunctional protein that serves as cross-linking enzyme and integrin-binding adhesion coreceptor for fibronectin on the cell surface. Previous work showed activation of small GTPase RhoA via enzymatic transamidation by cytoplasmic tTG. Here, we report an alternative nonenzymatic mechanism of RhoA activation by cell surface tTG. Direct engagement of surface tTG with specific antibody or the fibronectin fragment containing modules I(6)II(1,2)I(7-9) increases RhoA-GTP levels. Integrin-dependent signaling to RhoA and its downstream target Rho-associated coiled-coil containing serine/threonine protein kinase (ROCK) is amplified by surface tTG. tTG expression on the cell surface elevates RhoA-GTP levels in nonadherent and adherent cells, delays maximal RhoA activation upon cell adhesion to fibronectin and accelerates a rise in RhoA activity after binding soluble integrin ligands. These data indicate that surface tTG induces integrin clustering regardless of integrin-ligand interactions. This notion is supported by visualization of integrin clusters, increased susceptibility of integrins to chemical cross-linking, and biochemical detection of large integrin complexes in cells expressing tTG. In turn, integrin aggregation by surface tTG inhibits Src kinase activity and decreases activation of the Src substrate p190RhoGAP. Moreover, pharmacological inhibition of Src kinase reveals inactivation of Src signaling as the primary cause of elevated RhoA activity in cells expressing tTG. Together, these findings show that surface tTG amplifies integrin-mediated signaling to RhoA/ROCK via integrin clustering and down-regulation of the Src-p190RhoGAP regulatory pathway.
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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.