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Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin

The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding m...

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Autores principales: Akimov, Sergey S., Krylov, Dmitry, Fleischman, Laurie F., Belkin, Alexey M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169362/
https://www.ncbi.nlm.nih.gov/pubmed/10684262
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author Akimov, Sergey S.
Krylov, Dmitry
Fleischman, Laurie F.
Belkin, Alexey M.
author_facet Akimov, Sergey S.
Krylov, Dmitry
Fleischman, Laurie F.
Belkin, Alexey M.
author_sort Akimov, Sergey S.
collection PubMed
description The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.
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spelling pubmed-21693622008-05-01 Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin Akimov, Sergey S. Krylov, Dmitry Fleischman, Laurie F. Belkin, Alexey M. J Cell Biol Original Article The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading. The Rockefeller University Press 2000-02-21 /pmc/articles/PMC2169362/ /pubmed/10684262 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Akimov, Sergey S.
Krylov, Dmitry
Fleischman, Laurie F.
Belkin, Alexey M.
Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin
title Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin
title_full Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin
title_fullStr Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin
title_full_unstemmed Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin
title_short Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin
title_sort tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169362/
https://www.ncbi.nlm.nih.gov/pubmed/10684262
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