Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells
Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells(54 views) Soluri MF, Boccafoschi F, Cotella D, Moro L, Forestieri G, Autiero I, Cavallo L, Oliva R, Griffin M, Wang Z, Santoro C, Sblattero D
Paper type: Journal Article
, Research Support, Non-U. S. Gov'T
Impact factor: 0, 5-year impact factor: 0
Url: Not available.
Keywords: Animals
, Binding Sites
, Cell Adhesion
, Cell Movement
, Cultured
, Fibronectins Chemistry Genetics Metabolism
, Gtp-Binding Proteins Chemistry Genetics Metabolism
, Humans
, Mice
, Knockout
, Models, Molecular
, Protein Binding
, Protein Conformation
, Protein Domains
, Protein Glutamine Gamma Glutamyltransferase 2
, Signal Transduction
, Transglutaminases Chemistry Genetics Metabolism
, Extracellular Matrix
, Gelatin Binding Domain (gbd)
, Ovarian Cancer
Affiliations: Department of Health Sciences, University of Piemonte Orientale (UPO), Novara, Italy.
Interdisciplinary Research Center on Autoimmune Diseases (IRCAD), University of Piemonte Orientale (UPO), Novara, Italy.
Department of Pharmaceutical Sciences, University of Piemonte Orientale (UPO), Novara, Italy.
Physical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST) Catalysis Center (KCC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Department of Sciences and Technologies, University Parthenope of Naples, Naples, Italy.
Computer, Electrical, and Mathematical Sciences and Engineering (CEMSE) Division, Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
School of Life and Health Sciences, Aston University, Birmingham, United Kingdom
Department of Life Sciences, University of Trieste, Trieste, Italy.
References: Not available.
Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells
The interaction between the enzyme transglutaminase 2 (TG2) and fibronectin (FN) is involved in the cell-matrix interactions that regulate cell signaling, adhesion, and migration and play central roles in pathologic conditions, particularly fibrosis and cancer. A precise definition of the exact interaction domains on both proteins could provide a tool to design novel molecules with potential therapeutic applications. Although specific residues involved in the interaction within TG2 have been analyzed, little is known regarding the TG2 binding site on FN. This site has been mapped to a large internal 45-kDa protein fragment coincident with the gelatin binding domain (GBD). With the goal of defining the minimal FN interacting domain for TG2, we produced several expression constructs encoding different portions or modules of the GBD and tested their binding and functional properties. The results demonstrate that the I(8) module is necessary and sufficient for TG2-binding in vitro, but does not have functional effects on TG2-expressing cells. Modules I(7) and I(9) increase the strength of the binding and are required for cell adhesion. A 15-kDa fragment encompassing modules I(7-9) behaves as the whole 45-kDa GBD and mediates signaling, adhesion, spreading, and migration of TG2(+) cells. This study provides new insights into the mechanism for TG2 binding to FN.-Soluri, M. F., Boccafoschi, F., Cotella, D., Moro, L., Forestieri, G., Autiero, I., Cavallo, L., Oliva, R., Griffin, M., Wang, Z., Santoro, C., Sblattero, D. Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells.
Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells
Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells