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TG2, a novel extracellular protein with multiple functions

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Abstract

TG2 is multifunctional enzyme which can be secreted to the cell surface by an unknown mechanism where its Ca2+-dependent transamidase activity is implicated in a number of events important to cell behaviour. However, this activity may only be transient due to the oxidation of the enzyme in the extracellular environment including its reaction with NO probably accounting for its many other roles, which are transamidation independent. In this review, we discuss the novel roles of TG2 at the cell surface and in the ECM acting either as a transamidating enzyme or as an extracellular scaffold protein involved in cell adhesion. Such roles include its ability to act as an FN co-receptor for β integrins or in a heterocomplex with FN interacting with the cell surface heparan sulphate proteoglycan syndecan-4 leading to activation of PKCα. These different properties of TG2 involve this protein in various physiological processes, which if not regulated appropriately can also lead to its involvement in a number of diseases. These include metastatic cancer, tissue fibrosis and coeliac disease, thus increasing its attractiveness as both a therapeutic target and diagnostic marker.

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Abbreviations

TG2:

Tissue transglutaminase

TGs:

Transglutaminases

PDI:

Protein disulphide isomerase

TGFβ1:

Transforming growth factor β1

PLC:

Phospholipase C

FN:

Fibronectin

ECM:

Extracellular matrix

HOB:

Human osteoblasts

HSPGs:

Heparan sulphate proteoglycans

ERK1/2:

Extracellular signal-regulated kinase1/2

FITC:

Fluorescein isothiocyanate

FAK:

Focal adhesion kinase

HUVEC:

Human umbilical vein endothelial cells

siRNA:

Small interfering RNA

IL:

Interleukin

NF-κB:

Nuclear factor κB

TNF:

Tumour necrosis factor

TGM2:

TG2 gene

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

PDGFR:

Platelet-derived growth factor receptor

GPR56:

G-protein coupled receptor 56

MMP:

Matrix metalloproteinase

MT1-MMP:

Membrane type1 metalloproteinase

HFDF:

Human foreskin dermal fibroblasts

vSMC:

Vascular smooth muscle cells

OPN:

Osteopontin

BSP:

Bone sialoprotein

SPD:

Spermidine

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  1. School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B47ET, UK

    Zhuo Wang & Martin Griffin

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  1. Zhuo Wang
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Wang, Z., Griffin, M. TG2, a novel extracellular protein with multiple functions. Amino Acids 42, 939–949 (2012). https://doi.org/10.1007/s00726-011-1008-x

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