Thrombopoietin regulates IEX-1 gene expression through ERK-induced AML1 phosphorylation

摘要: The extracellular signal-regulated kinases (ERKs) are required for thrombopoietin (TPO) functions on hematopoietic cells, but the ERKs targets involved remain unknown. Here we show that regulation of immediate early gene X-1 (IEX-1), identified as an ERK substrate in response to TPO, was mediated by ERK-dependent phosphorylation AML1. addition TPO UT7-Mpl cells and primary megakaryocytes induced expression IEX-1. Neither erythropoietin (EPO) nor granulocyte macrophage-colony stimulating factor (GM-CSF) able activate IEX-1 cells. a transcriptional activation promoter AML1-binding site located at -1068. direct involvement AML1 shown both use mutants shRNA experiments targeting endogenous Finally, ability induce inhibited U0126, specific inhibitor activator MEK activity be modulated through phosphorylation. Taken together, these data suggest plays role modulating regulates TPO-mediated