SHP2 tyrosine phosphatase stimulates CEBPA gene expression to mediate cytokine-dependent granulopoiesis.

ABSTRACT: G-CSF signals contribute to granulocyte lineage specification. We previously found that G-CSF induces SHP2 tyrosine phosphorylation and that chemical inhibition of SHP1/SHP2 reduces CFU-G and prevents G-CSF but not M-CSF activation of ERK. We now find that SHP2 shRNA knockdown in the 32Dcl3 granulocytic line reduces ERK activation, diminishes CEBPA protein and RNA expression and promoter histone acetylation, and inhibits granulopoiesis. Exogenous, shRNA-resistant SHP2 rescues these effects of SHP2 knockdown, exogenous C/EBPα rescues granulocytic markers, and exogenous RUNX1 rescues C/EBPα. 32Dcl3 lines with knockdown of ERK1 and ERK2 retain normal levels of C/EBPα and differentiate normally in G-CSF despite also having reduced proliferation. SHP2 knockdown reduces CEBPA levels in lineage-n

SUBMITTER: Zhang L 

PROVIDER: S-EPMC3162355 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature