CARBONYL-COMPOUNDS CROSS-LINK CELLULAR PROTEINS AND ACTIVATE PROTEIN-TYROSINE KINASE P60(C-SRC)

Glyoxal, a dicarbonyl compound, is produced under oxidative stress by the autoxidation of glucose and reacts with the protein amino group to form Schiff base. In vitro treatment of murine thymocytes and fibrobl asts with glyoxal induced extensive tyrosine phosphorylation of multip le proteins, which was drastically inhibited by the addition of OPB-91 95, an inhibitor of the carbonyl reaction with proteins. Glyoxal induc ed cross-linking of a number of cellular proteins, including glycosylp hosphatidylinositol (GPI)-anchored cell surface Thy-1. We then demonst rated that treatment of cells with glyoxal promptly induced activation of non-receptor protein-tyrosine kinase c-Src, which was partially in hibited by OPB-9195. It is suggested from these results that carbonyl amine reaction quickly activates c-Src, possibly through cross-linkage of GPI-anchored proteins or putative specific receptors. J. Cell. Bio chem. 72:1-7, 1999. (C) 1999 Wiley-Liss, Inc.