title: Transglutaminase and epsilon-(gamma-glutamyl) lysine isopeptide bonds in eukaryotic cells.
abstract: Transglutaminase activity was reduced in malignant hepatoma, virus-transformed human and hamster cells, and chemically transformed mouse cells when compared to normal counterparts. The reduction in enzyme activity reflected the presence of fewer transglutaminase molecules in transformed cells. Greater amounts of the enzyme activity were particulate-associated in confluent and arrested normal human cells. Indirect immunofluorescence studies with antibody to cellular transglutaminase demonstrated the presence of transglutaminase in Triton X-100-insoluble material. A parallel between pericellular fibronectin and transglutaminase (TGase) was demonstrated. Normal human and mouse cells that elicited contact inhibition of growth and had the high TGase activity also had more epsilon-(gamma-glutamyl) lysine isopeptide bonds than transformed counterparts. Similarly nonproliferating human cells had higher transglutaminase activity and isopeptide levels than did proliferating populations. These results suggest that isopeptide bond formation stabilizes the cell membrane and contributes to a nonproliferating state. Inhibition of isopeptide formation should therefore lead to a mitogenic response. Preliminary results support such a relationship. A model depicting control of isopeptide formation at either enzyme or substrate level is presented.
mesh_terms: D000818:Animals; D002455:Cell Division; D002477:Cells / Q000201:enzymology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005057:Eukaryotic Cells / Q000201:enzymology*; D005353:Fibronectins / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D005971:Glutamates; D008565:Membrane Proteins; D005723:gamma-Glutamyltransferase; D008239:Lysine