C/EBPalpha S248A mutation reduces granulocytic differentiation in human leukemic K562 cells.

Phosphorylation of C/EBPalpha can either lead to granulocytic differentiation or a block in granulopoiesis. This dichotomy in effect is dependent on the upstream signaling pathway and the phosphorylation site in C/EBPalpha. Ras signaling induced phosphorylation of S248 residue of C/EBPalpha is known to enhance granulocytic differentiation. In this study, using beta-estradiol inducible stable cell lines we show that the point mutation of phosphorylation site S248 in C/EBP disrupts the CD11b and GCSFr expression and subsequently reduces the differentiation of leukemic K562 cells. Based on our observations in the present study, we conclude that S248A mutation of C/EBPalpha leads to a reduction of granulocytic differentiation markers and a block in differentiation at the morphological level.