The cellular response to transglutaminase-cross-linked collagen

Chau, David; Collighan, Russell; Verderio, Elisabetta; Addy, Victoria L.; Griffin, Martin

doi:10.1016/j.biomaterials.2005.04.017

Cited by 192 publications

(168 citation statements)

References 41 publications

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“…One of the important functions of TG2 pertains to its role in the extracellular environment where it may influence both cell adhesion (Akimov et al 2000;Telci et al 2008;Verderio et al 2003) and matrix accumulation/stability (Akimov and Belkin 2001;Chau et al 2005). In all TG2-transfected clones, TG2 was found at the cell surface, but in keeping with our earlier studies (Balklava et al 2002;Gaudry et al 1999), only in the clones transfected with the active wild type enzyme was it found deposited in the extracellular matrix (ECM).…”

Section: Discussionsupporting

confidence: 66%

“…In the extracellular environment, TG2 can also function through its Ca 2? -activated transamidating activity to increase the rate of deposition of ECM proteins such as FN and collagen I (Shweke et al 2008;Verderio et al 1999;Yuan et al 2007), leading to accumulation and changes in the ECM influencing both cell adhesion and differentiation (Chau et al 2005;Johnson et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26

et al. 2010

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The multifunctional enzyme tissue transglutaminase (TG2) is reported to both mediate and inhibit tumour progression. To elucidate these different roles of TG2, we established a series of stable-transfected mouse colon carcinoma CT26 cells expressing a catalytically active (wild type) and a transamidating-inactive TG2 (Cys277Ser) mutant. Comparison of the TG2-transfected cells with the empty vector control indicated no differences in cell proliferation, apoptosis and susceptibility to doxorubicin, which correlated with no detectable changes in the activation of the transcription factor NF-jB. TG2-transfected cells showed increased expression of integrin b3, and were more adherent and less migratory on fibronectin than control cells. Direct interaction of TG2 with b3 integrins was demonstrated by immunoprecipitation, suggesting that TG2 acts as a coreceptor for fibronectin with b3 integrins. All cells expressed the same level of TGFb receptors I and II, but only cells transfected with active TG2 had increased levels of TGFb1 and matrix-deposited fibronectin, which could be inhibited by TG2 site-directed inhibitors. Moreover, only cells transfected with active TG2 were capable of inhibiting tumour growth when compared to the empty vector controls. We conclude that in this colon carcinoma model increased levels of active TG2 are unfavourable to tumour growth due to their role in activation of TGFb1 and increased matrix deposition, which in turn favours increased cell adhesion and a lowered migratory and invasive behaviour.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26

et al. 2010

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“…Our initial objective in this paper was, therefore, to identify the HSPG involved in this interaction with TG-FN and to determine whether this interaction is mediated directly via binding of the HSPG to TG2 as TG2 is known to have a high affinity for heparin (15). First we show that CHO-K1 cells deficient in synthesis of HS chains did not attach or spread on TG-FN in an RGD-independent manner, confirming the importance of HS chains in this process.…”

Section: Discussionmentioning

confidence: 99%

“…TG2 can enhance the cell attachment and spreading of a number of different cell types through the modification of ECM proteins by their cross-linking (15,16). However, recent reports also describe a non-transamidating mechanism whereby TG2 acts as a novel cell adhesion protein (6,17) thought to involve direct interaction with a variety of integrin receptors.…”

mentioning

confidence: 99%

Fibronectin-Tissue Transglutaminase Matrix Rescues RGD-impaired Cell Adhesion through Syndecan-4 and β1 Integrin Co-signaling

Telci

Wang

et al. 2008

Journal of Biological Chemistry

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Heterotropic association of tissue transglutaminase (TG2) with extracellular matrix-associated fibronectin (FN) can restore the adhesion of fibroblasts when the integrin-mediated direct binding to FN is impaired using RGD-containing peptide. We demonstrate that the compensatory effect of the TG-FN complex in the presence of RGD-containing peptides is mediated by TG2 binding to the heparan sulfate chains of the syndecan-4 cell surface receptor. This binding mediates activation of protein kinase C␣ (PKC␣) and its subsequent interaction with ␤ 1 integrin since disruption of PKC␣ binding to ␤ 1 integrins with a cell-permeant competitive peptide inhibits cell adhesion and the associated actin stress fiber formation. Cell signaling by this process leads to the activation of focal adhesion kinase and ERK1/2 mitogen-activated protein kinases. Fibroblasts deficient in Raf-1 do not respond fully to the TG-FN complex unless either the full-length kinase competent Raf-1 or the kinase-inactive domain of Raf-1 is reintroduced, indicating the involvement of the Raf-1 protein in the signaling mechanism. We propose a model for a novel RGD-independent cell adhesion process that could be important during tissue injury and/or remodeling whereby TG-FN binding to syndecan-4 activates PKC␣ leading to its association with ␤ 1 integrin, reinforcement of actin-stress fiber organization, and MAPK pathway activation. Tissue transglutaminase (TG2)2 belongs to a family of enzymes that in the presence of Ca 2ϩ catalyze the post-translational modification of proteins either by covalent cross-linking or through the incorporation of primary amines. TG2 has a GTP binding/hydrolysis site that negatively modulates the Ca 2ϩ -dependent transamidating activity of the enzyme by obstructing access to the active site (1). As a consequence, the enzyme is likely to be inactive under normal Ca 2ϩ homeostasis. TG2 localizes mainly in the cytoplasm, yet recent reports also suggest its presence in the nucleus, mitochondria, at the cell surface, and in the extracellular matrix (ECM) (1-3). TG2 is translocated to the plasma membrane and was subsequently deposited into the ECM via a non-classical secretory mechanism reportedly dependent on active site conformation and on an intact N-terminal ␤-sandwich domain (4, 5) as well as on its possible association with integrins (6). Deposition of the enzyme into the ECM after cell damage and stress is important in the remodeling and/or stabilization of the several ECM proteins, such as FN (7,8). FN is particularly interesting since TG2 binds to this ECM protein with high affinity promoting wideranging effects on cell-matrix interactions, including the regulation of cell adhesion and migration, matrix assembly, and adhesion-dependent signaling (6,7,9).Cell adhesion to FN involves a series of coordinated signaling events orchestrated by numerous transmembrane receptors including the integrins and the superfamily of cell-surface proteoglycans (10, 11). The identity of the receptor-ligand pairing defines the composition of f...

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“…Infusions of factor XIII to reduce bleeding during cardiopulmonary bypass surgery has been discussed. Transglutaminase-modified matrices could be used to improved physical and biological properties or to incorporate specific agents into engineered tissues (188)(189)(190).…”

Section: Diagnostic and Therapeutic Implications Of Transglutaminasesmentioning

confidence: 99%

Roles of transglutaminases in cardiac and vascular diseases

Sane

Kontos²,

Greenberg³

2007

Front Biosci

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All transglutaminases share the common enzymatic activity of transamidation, or the cross-linking of glutamine and lysine residues to form N epsilon (gamma-glutamyl) lysyl isopeptide bonds. The plasma proenzyme factor XIII is responsible for stabilizing the fibrin clot against physical and fibrinolytic disruption. Another member of the transglutaminase family, tissue transglutaminase or TG2 is abundantly expressed in cardiomyocytes, vascular cells and macrophages. The transglutaminases have a variety of functions independent of their transamidating activity. For example, TG2 binds and hydrolyzes GTP, thereby fostering signal transduction by several G protein coupled receptors. Accumulating evidence points to novel roles for factor XIII and TG2 in cardiovascular biology including: (a) modulating platelet activity, (b) regulating glucose control, (c) contributing to the development of hypertension, (d) influencing the progression of atherosclerosis, (e) regulating vascular permeability and angiogenesis (f) and contributing to myocardial signaling, contractile activity and ischemia/reperfusion injury. In this review, we summarize the cardiovascular biology of two members of the family of transglutaminases, Factor XIII and TG2.

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The cellular response to transglutaminase-cross-linked collagen

Cited by 192 publications

References 41 publications

The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26

The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26

Fibronectin-Tissue Transglutaminase Matrix Rescues RGD-impaired Cell Adhesion through Syndecan-4 and β1 Integrin Co-signaling

Roles of transglutaminases in cardiac and vascular diseases

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