Activation of STAT5 during EPO-directed suppression of apoptosis

The ligand-dependent activation of the JAK/STAT (JanuskinaseiSignal Transdu cer and Activator of Transcription) pathway has been implicated in the expl anation of cytokine-specific regulation of gene expression. Previous studie s have reported conflicting results on the role of the transcription factor STATS in erythropoietin (EPO)-induced cellular responses. In this study we focused on the functional importance of STATS docking sites in the intrace llular EPO receptor (EPOR) domain for the mediation of antiapoptotic activi ties. We demonstrate that EPO-dependent survival of erythroleukemic cell li nes is accompanied by sustained STATS DNA-binding activity. The role of sin gle tyrosine residues was dissected by the analysis of myeloid FDCP-1 cells stably expressing mutant EPOR proteins. The data show that receptors havin g a high potential to mediate antiapoptotic signals also effectively activa te STATS, whereas receptors lacking STATS docking sites are diminished in b oth activities. We conclude that the transcription factor STATS is function ally implicated in the EPO-dependent survival of cells. (C) 2000 Elsevier S cience Inc. All rights reserved.