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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
Author(s) -
Soluri Maria Felicia,
Boccafoschi Francesca,
Cotella Diego,
Moro Laura,
Forestieri Gabriela,
Autiero Ida,
Cavallo Luigi,
Oliva Romina,
Griffin Martin,
Wang Zhuo,
Santoro Claudio,
Sblattero Daniele
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800054rrr
Subject(s) - tissue transglutaminase , fibronectin , adhesion , microbiology and biotechnology , cell adhesion , domain (mathematical analysis) , fibronectins , chemistry , biology , biochemistry , enzyme , extracellular matrix , mathematics , organic chemistry , mathematical analysis
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. FASEB J. 33, 2327–2342 (2019). www.fasebj.org