Transglutaminase gene products

The invention provides a nucleotide sequence comprising at least a portion of the nucleotide sequence of FIG. 10A, FIG. 6B or FIG. 10A or FIG. 10B; nucleotides which hybridise to the nucleotide sequences of FIG. 6A, FIG. 6B or FIG. 10A or FIG. 10B; nucleotides which are degenerate to the nucleotide sequences of FIG. 6A, FIG. 6B or FIG. 10A or FIG. 10B; all of which nucleotides encode a polypeptide having transglutaminase activity

Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the genes encoding transglutaminase X and a novel gene family member, Transglutaminase Z

We isolated and characterized the gene encoding human transglutaminase (TG)X (TGM5) and mapped it to the 15q15.2 region of chromosome 15 by fluorescence in situ hybridization. The gene consists of 13 exons separated by 12 introns and spans about 35 kilobases. Further sequence analysis and mapping showed that this locus contained three transglutaminase genes arranged in tandem: EPB42 (band 4.2 protein), TGM5, and a novel gene (TGM7). A full-length cDNA for the novel transglutaminase (TGZ) was obtained by anchored polymerase chain reaction. The deduced amino acid sequence encoded a protein with 710 amino acids and a molecular mass of 80 kDa. Northern blotting showed that the three genes are differentially expressed in human tissues. Band 4.2 protein expression was associated with hematopoiesis, whereas TGX and TGZ showed widespread expression in different tissues. Interestingly, the chromosomal segment containing the human TGM5, TGM7, and EPB42 genes and the segment containing the genes encoding TGC,TGE, and another novel gene (TGM6) on chromosome 20q11 are in mouse all found on distal chromosome 2 as determined by radiation hybrid mapping. This finding suggests that in evolution these six genes arose from local duplication of a single gene and subsequent redistribution to two distinct chromosomes in the human genome

Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses

Tissue transglutaminase (TG2) affects cell-matrix interactions in cell spreading, migration and extracellular matrix (ECM) reorganisation. Using fibroblasts deficient in TG2 or overexpressing normal or crosslinking-deficient enzyme, we show that the extracellular crosslinking activity and intracellular G-protein function in signal transduction contribute differentially to regulation of cell-matrix interactions. TG2-deficient cells displayed normal attachment but delayed spreading on ECM substrata and defects in motility unrelated to crosslinking. Blocking antibodies to TG2 failed to induce similar defects in normal fibroblasts. TG2-deficient fibroblasts had defects in focal adhesion turnover and stress fibre formation, showed changes in focal adhesion kinase (FAK) phosphorylation and failed to activate protein kinase C (PKC). Phospholipase C (PLC) and PKC inhibitors blocked spreading of normal fibroblasts whilst PKC activators induced spreading in TG2-deficient cells. In contrast, ECM remodelling was not only compromised by TG2 deficiency but also by overexpression of dominant negative enzyme and TG inhibitors. TG2 activity increased matrix tension and was required for membrane type 1-MMP (MT1-MMP)-dependent activation of MMP-2. Our results demonstrate that TG2 is involved in the control of dynamic adhesion formation in cell spreading and migration via regulation of phospholipase C activity. By virtue of its crosslinking activity, the enzyme plays a central role in regulating ECM remodelling