FAS, also referred to as CD95 or APO-1, is a type I transmembrane protein that plays a central role mediating viral immunity. TIA-1 and TIAR are two closely related proteins that possess three RRMs (RNA recognition motifs), designated RRM 1, 2 and 3. Although both TIA-1 and TIAR are thought to function as mediators of apoptotic cell death, their specific roles in such pathways are unknown. Unlike TIA-1, which is found in the granules of cytotoxic lymphocytes, TIAR expression is limited to the nucleus and found in a much broader range of cells including, but not limited to, cells of hematopoietic origin. TIAR is translocated to the cytoplasm shortly after FAS ligation and this event immediately proceeds the onset of DNA fragmentation. A novel serine/threonine kinase that is activated as a result of FAS ligation, designated FAST (FAS-activated serine/threonine), shows kinase specificity towards both TIA-1 and TIAR. In unstimulated Jurkat cells, FAST resides in the cytoplasm as a highly phosphorylated protein and is quickly dephosphorylated and activated in response to stimulated FAS.
