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.
Singh
Sheo M
SM
Bone Marrow Transplantation Section, State Center for Cell and Gene Therapy, Department of Internal Medicine IV, Martin-Luther-University, Ernst Grube Str. 40, Halle 06097, Germany.
Trivedi
A K
AK
Behre
Gerhard
G
D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D009154:Mutation; D010766:Phosphorylation; D013329:Structure-Activity Relationship
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human