DUAL FUNCTIONS OF TRANSGLUTAMINASE IN NOVEL CELL-ADHESION

Transglutaminases (TGases) are enzymes which catalyze cross-link forma tion between glutamine residues and lysine residues in substrate prote ins, In the present study, we report for the first time that a represe ntative enzyme, blood coagulation factor XIIIa (FXIIIa), is capable of mediating adhesion of various cells, When coated on plastic surfaces FXIIIa promoted adhesion and spreading of various cells of both normal and tumor origin, in a concentration-dependent manner, The adhesion w as not inhibited by antibodies against possible contaminants in the en zyme preparation such as fibronectin and vitronectin, but was complete ly inhibited by a polyclonal antibody against the enzyme, Therefore, i f there were any contaminating cell adhesive substrates in the enzyme preparation, they cannot account for the observed cell adhesion to the enzyme; FXIIIa itself mediates the cell adhesion, Furthermore, phosph orylation of tyrosine residues in 120 kDa and 70 kDa proteins was clea rly shown in human fibroblasts adhering to the enzyme, Formation of ac tin stress fibers was also unambiguously observed in the adhering cell s, These biochemical reactions, which are also observed when cells adh ere to a typical cell adhesion protein, fibronectin, are believed to b e of importance in the process of cell adhesion, This adhesion activit y of FXIIIa was dependent on its TGase activity, because both a modifi cation of the active center cysteine with iodoacetamide and the additi on of ammonium ion abolished the cell adhesion activity along with the enzyme activity, The cell adhesion to fibronectin, however, was not a ffected by these treatments, The effects of various anti-integrin anti bodies suggested that both alpha v beta 3 and beta 1 family integrins participated in the cell adhesion to FXIIIa, Taken together, these dat a demonstrate for the first time that there is a unique TGase activity -mediated cell adhesion, This novel function of the enzyme may be of p hysiological importance.