HUMAN ERG-2 PROTEIN IS A PHOSPHORYLATED DNA-BINDING PROTEIN - A DISTINCT MEMBER OF THE ETS FAMILY

We describe the identification of the ERG-2 gene products using an ant ibody raised against recombinant human ERG-2 protein. ERG-2 is a nucle ar phosphoprotein and binds to purine-rich sequences (C/G)(C/a)GG-AA(G /a)T. ERG-2 protein, with a half-life of 21 h, is considerably more st able than the short-lived ETS-1 or ETS-2 proteins. Its phosphorylation is stimulated by phorbal myristate acetate (PMA), but not by Ca2+ ion -phore treatment. ETS-1 protein is phosphorylated by Ca2+-dependent ev ents, whereas ERG-2 protein is phosphorylated by activation of protein kinase C, suggesting their involvement in distinct signal transductio n mechanisms. The expression of ERG-2 protein is restricted to few cel l types and is high in early myeloid cells, indicating that it may fun ction at an early stage of hematopoietic lineage determination. The DN A-binding sequence for ERG-2 protein is identified by using a random o ligonucleotide selection procedure. The selected sequence is very simi lar to the binding sequence determined for human ETS-1 using the same method. Like other ets proteins, ERG-2 is a sequence-specific DNA-bind ing protein and is expressed at higher levels in early myeloid cells t han in mature lymphoid cells. These results suggest that it may act as a regulator of genes required for maintenance and/or differentiation of early hematopoietic cells.