Protein-tyrosine phosphatase PTP epsilon C inhibits Jak-STAT signaling anddifferentiation induced by interleukin-6 and leukemia inhibitory factor inM1 leukemia cells

We engineered and expressed bath a wild-type and mutant cytosolic isoform o f PTP epsilon (PTP epsilon C) in murine M1 leukemic cells, which can be ind uced to growth arrest and monocytic differentiation by interleukin (IL)-6 a nd leukemia inhibitory factor (LIF). Forced expression of PTP epsilon C inh ibited IL-6- and LIF-induced monocytic differentiation and apoptosis in M1 cells, whereas expression of PTP epsilon M, a transmembrane isoform of PTP epsilon, did not. PTP epsilon C expression resulted in lower levels of IL-6 -induced tyrosine phosphorylation of Jak1, Tyk2, gp130, and Stat3 compared with parent cells. In MI transfectants expressing an inactive mutant of PTP epsilon C, both tyrosine phosphorylation and apoptosis induced by IL-6- an d LIF were potentiated rather than inhibited. These results suggest an impo rtant role for PTP epsilon C in negative regulation of IL-6- and LIF-induce d Jak-STAT signaling.