Analysis of tissue transglutaminase function in the migration of Swiss 3T3 fibroblasts:the active-state conformation of the enzyme does not affect cell motility but is important for its secretion


Increasing evidence suggests that tissue transglutaminase (tTGase; type II) is externalized from cells, where it may play a key role in cell attachment and spreading and in the stabilization of the extracellular matrix (ECM) through protein cross-linking. However, the relationship between these different functions and the enzyme's mechanism of secretion is not fully understood. We have investigated the role of tTGase in cell migration using two stably transfected fibroblast cell lines in which expression of tTGase in its active and inactive (C277S mutant) states is inducible through the tetracycline-regulated system. Cells overexpressing both forms of tTGase showed increased cell attachment and decreased cell migration on fibronectin. Both forms of the enzyme could be detected on the cell surface, but only the clone overexpressing catalytically active tTGase deposited the enzyme into the ECM and cell growth medium. Cells overexpressing the inactive form of tTGase did not deposit the enzyme into the ECM or secrete it into the cell culture medium. Similar results were obtained when cells were transfected with tTGase mutated at Tyr(274) (Y274A), the proposed site for the cis,trans peptide bond, suggesting that tTGase activity and/or its tertiary conformation dependent on this bond may be essential for its externalization mechanism. These results indicate that tTGase regulates cell motility as a novel cell-surface adhesion protein rather than as a matrix-cross-linking enzyme. They also provide further important insights into the mechanism of externalization of the enzyme into the extracellular matrix.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences > Chronic and Communicable Conditions
Aston University (General)
Additional Information: This research was originally published in the Journal of Biological Chemistry. Zita Balklava, Elisabetta Verderio, Russell Collighan, Stephane Gross, Julian Adams and Martin Griffin. Analysis of Tissue Transglutaminase Function in the Migration of Swiss 3T3 Fibroblasts THE ACTIVE-STATE CONFORMATION OF THE ENZYME DOES NOT AFFECT CELL MOTILITY BUT IS IMPORTANT FOR ITS SECRETION. J. Biol. Chem. 2002; Vol 277, 16567-16575. © the American Society for Biochemistry and Molecular Biology
Uncontrolled Keywords: transglutaminase,cell migration
Publication ISSN: 1083-351X
Last Modified: 27 Jun 2024 07:37
Date Deposited: 19 Aug 2019 08:49
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Related URLs: http://www.jbc. ... /16567.abstract (Publisher URL)
PURE Output Type: Article
Published Date: 2002-02-26
Authors: Balklava, Zita (ORCID Profile 0000-0001-9039-9710)
Verderio, Elisabetta
Collighan, Russell (ORCID Profile 0000-0003-0204-5125)
Gross, Stephane (ORCID Profile 0000-0002-0867-8866)
Adams, Julian
Griffin, Martin (ORCID Profile 0000-0003-3824-306X)



Version: Published Version

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