PREVENTION OF APOPTOSIS IN J2E ERYTHROID-CELLS BY ERYTHROPOIETIN - INVOLVEMENT OF JAK2 BUT NOT MAP KINASES

The J2E erythroid cell line, transformed by retroviral v-raf/v-myc onc ogenes, proliferates and differentiates in response to erythropoietin. Here we show that J2E cells undergo apoptosis rapidly after serum wit hdrawal and that only erythropoietin of seven growth factors tested, c ould protect the cells from death. The role of JAK2 and MAP kinases in transmitting viability signals initiated by erythropoietin was examin ed in these cells. Despite constituitive raf kinase activity, phosphor ylation of MAP kinases fell after serum withdrawal. However, an antise nse oligonucleotide strategy revealed that JAK2, but not the MAP kinas es, was involved in transmitting signals to maintain the viability of J2E cells. Several cell cycle proteins and transcription factors were also studied; although c-jun rose sharply during apoptosis, erythropoi etin could not suppress this increase. It was concluded that erythropo ietin-induced protection from apoptosis involved JAK2, but not MAP kin ases or c-jun.