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

Sheo M Singh; A K Trivedi; Gerhard Behre

doi:10.1016/j.bbrc.2008.02.090

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

Biochem Biophys Res Commun. 2008 May 2;369(2):692-4. doi: 10.1016/j.bbrc.2008.02.090. Epub 2008 Feb 25.

Authors

Sheo M Singh¹, A K Trivedi, Gerhard Behre

Affiliation

¹ 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.

PMID: 18302931
DOI: 10.1016/j.bbrc.2008.02.090

Abstract

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.

MeSH terms

CCAAT-Enhancer-Binding Proteins / genetics
CCAAT-Enhancer-Binding Proteins / metabolism*
Cell Differentiation*
Granulocytes / cytology*
Granulocytes / metabolism*
Humans
K562 Cells
Mutation
Phosphorylation
Structure-Activity Relationship

Substances

CCAAT-Enhancer-Binding Proteins
CEBPA protein, human