A PHYSICAL INTERACTION BETWEEN THE CELL-DEATH PROTEIN FAS AND THE TYROSINE KINASE P59(FYNT)

The Fas antigen (Apol/CD95) is a transmembrane protein belonging to th e nerve growth factor receptor family. It is expressed on a variety of cells, including activated T lymphocytes. Ligation of Fas with its na tural ligand or with anti-Fas antibodies often results in the apoptoti c death of the cell, making Fas an important mediator of down-regulati ng immune responses. The signal transduction pathways utilized by Fas are currently unknown, although tyrosine kinase activity has recently been strongly implicated. Here, we report that the tyrosine kinase p59 (fyn) physically associates with Fas in Fas sensitive cells. In additi on, we show that activated T lymphocytes from fyn knockout mice exhibi t elevated lifespans and reduced apoptosis in vitro compared to their normal counterparts. Furthermore, activated T lymphocytes from the fyn - deficient mice are less sensitive to killing by both anti-Fas antibo dy and Fas-ligand cytotoxic T cells. These results suggest that p59(fy n) plays an important role in Fas signal transduction.