Cell Surface Tissue Transglutaminase-induced Activation of Phosphoinositol 3-Kinase/Akt Pathway / 체질인류학회지

ABSTRACT

Multifunctional tissue transglutaminase (tTGase) is found in the cytoplasm and cell surface, as well as in the extracellular matrix. However, it is difficult to determine the exact function of tTGase in each cell compartment. This study focused on the potential role of cell surface tTGase in the process of "outside-in" signal transduction. Immunofluorescence study and western blotting was performed to localize the overexpression of tTGase. tTGaseoverexpressed H9c2/tTGase cells were treated with anti-tTGase antibody to evaluate the potential functions of tTGase on the outside-in signal process. The tTGase level markedly increased in each cell compartment and the culture media of H9c2/tTGase cells that show overexpression of tTGases. Anti-tTGase monoclonal antibody reduced tTGase levels in the whole lysate of H9c2/tTGase cells, and concomitantly increased the activity of the Akt. The results suggest that the cell surface expression of tTGase may be associated with an intracellular signaling pathway via the phosphoinositol-3 kinase/Akt. Phosphorylation of mitogen activated protein kinase family, ERK1/2, and Jun N-terminal Kinase (JNK), was also inhibited in the anti-tTGase antibody-treated H9c2/tTGase cells. These results suggest that cell surface tTGase may regulate intracellular signaling pathways in an autocrine or paracrine manner.