Protein kinase C-zeta overexpression induces erythroid phenotype in the monocytic leukaemia cell line U937.

Abstract:

:Previous studies have established that protein kinase C-zeta (PKC-zeta) is critical for neuronal cell differentiation. However, the role of PKC-zeta in haematopoietic cell differentiation is less clear. In this study, we have investigated the influence of PKC-zeta overexpression on the phenotype of the human monocytic U937 leukaemic cells. In two PKC-zeta-overexpressing clones (U937 zetaJ and U937 zetaB), PKC-zeta expression levels and activity were three to fourfold higher, and the enzyme accumulated both in the cytoplasm and in the nucleus compared with U937 control cells. PKC-zeta-overexpressing U937 cells exhibited an erythroid phenotype characterized by high levels of glycophorin A, cell haemoglobinization, increased GATA-1 transcripts and protein expression, compared with controls. Immunoprecipitation studies revealed that GATA-1 protein was constitutively phosphorylated in PKC-zeta-overexpressing cells. Moreover, GATA-1 did not interact with PKC-zeta but interacted with ERK1, which was constitutively activated and accumulated in the nucleus of U937 zetaJ. However, ERK1 phosphorylation inhibition by PD098059 did not influence either GATA-1 phosphorylation or GATA-1/ERK1 interaction. Collectively, these results suggest a model in which PKC-zeta induces MEK-dependent ERK1 activation, ERK1 translocation to the nucleus, GATA-1/ERK1 interaction and ERK1-independent GATA-1 phosphorylation resulting in GATA-1 accumulation. To conclude, this study provides evidence for the role of PKC-zeta in erythroid gene regulation.

journal_name

Br J Haematol

authors

Mansat-De Mas V,de Thonel A,Gaulin V,Demur C,Laurent G,Quillet-Mary A

doi

10.1046/j.1365-2141.2002.03625.x

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

646-53

issue

2

eissn

0007-1048

issn

1365-2141

pii

3625

journal_volume

118

pub_type

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