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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-7-25
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
646-53
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Protein kinase C-zeta overexpression induces erythroid phenotype in the monocytic leukaemia cell line U937.
pubmed:affiliation
Institut National de la Santé et de la Recherche Médicale (INSERM) E9910, Institut Claudius Régaud, 20 Rue du pont Saint-Pierre, 31052 Toulouse Cedex, France. demas.v@chu-toulouse.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't