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© The Rockefeller University Press, 0021-9525/2000//825 $5.00
The Journal of Cell Biology, Volume 148, Number 4, , 2000 825-838


Original Article

Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin



Sergey S. Akimova, Dmitry Krylova, Laurie F. Fleischmana, and Alexey M. Belkina

a Department of Biochemistry, American Red Cross, Rockville, Maryland 20855
Department of Biochemistry, J.H. Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855.(301) 738-0794(301) 738-0725

belkina{at}usa.redcross.org

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.

Key Words: adhesion • integrins • tissue transglutaminase • fibronectin • focal adhesions



© 2000 The Rockefeller University Press

Abbreviations used in this paper: ECM, extracellular matrix; FAK, focal adhesion kinase; Fn, fibronectin; FXIIIa, factor XIII; HEL, human erythroleukemia; TPA, 12-O-tetradecanoylphorbol 13-acetate; tTG, tissue transglutaminase.



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