SHP1 protein tyrosine phosphatase negatively modulates erythroid differentiation and suppression of apoptosis in J2E erythroleukemic cells

The SH2 domain-containing tyrosine phosphatase SHP1 is known to play a cruc ial role in the regulation of hematopoiesis. It has been shown previously t hat SHP1 associates with the activated erythropoietin receptor (EPOR) and n egatively regulates mitogenic signaling. To further elucidate the role of S HP1 in erythropoietin (EPO)-induced cellular responses we employed J2E eryt hroleukemic cells as a model for erythroid maturation and cytokine-triggere d suppression of apoptosis. Our data indicate that overexpressed SHP1 inhib its both EPO-induced differentiation as well as prevention of apoptosis, Th e specific signaling pathways responsible are not unraveled so far. Therefo re, we analyzed the involvement of SHP1 in two established EPO-stimulated p athways, the JAK/STAT and the MAP kinase cascades, by transient coexpressio n of reporter constructs containing binding sites for transcription factors targeted by these pathways and a SHP1 cDNA. Both pathways are inhibited by SHP1 as indicated by the lower induction of reporter gene activity. In con clusion, SHP1 regulates the transcriptional activity stimulated by the EPO- induced JAK/STAT and MAPK pathways and is involved in the signaling machine ry responsible for erythroid differentiation and suppression of apoptosis.