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

被引:10
作者
Mansat-De Mas, V
de Thonel, A
Gaulin, V
Demur, C
Laurent, G
Quillet-Mary, A
机构
[1] Inst Claudius Regaud, INSERM E9910, F-31052 Toulouse, France
[2] CHU Purpan, Hematol Lab, Toulouse, France
[3] CHU Purpan, Serv Hematol, Toulouse, France
关键词
PKC-zeta; erythroid phenotype; GATA-1; ERK-1; U937; cells;
D O I
10.1046/j.1365-2141.2002.03625.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:646 / 653
页数:8
相关论文
共 42 条
[1]   Regulation of NF-κB RelA phosphorylation and transcriptional activity by p21ras and protein kinase Cζ in primary endothelial cells [J].
Anrather, J ;
Csizmadia, V ;
Soares, MP ;
Winkler, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (19) :13594-13603
[2]   Lineage-restricted expression of protein kinase C isoforms in hematopoiesis [J].
Bassini, A ;
Zauli, G ;
Migliaccio, G ;
Migliaccio, AR ;
Pascuccio, M ;
Pierpaoli, S ;
Guidotti, L ;
Capitani, S ;
Vitale, M .
BLOOD, 1999, 93 (04) :1178-1188
[3]   Regulation of caspase activation and cis-diamminedichloroplatinum(II)-induced cell death by protein kinase C [J].
Basu, A ;
Akkaraju, GR .
BIOCHEMISTRY, 1999, 38 (14) :4245-4251
[4]  
Bearzatto A, 2000, CANCER RES, V60, P3262
[5]   Evidence for a role of MEK and MAPK during signal transduction by protein kinase C zeta [J].
Berra, E ;
DiazMeco, MT ;
Lozano, J ;
Frutos, S ;
Municio, MM ;
Sanchez, P ;
Sanz, L ;
Moscat, J .
EMBO JOURNAL, 1995, 14 (24) :6157-6163
[6]   Accumulation of catalytically active PKC-ζ into the nucleus of HL-60 cell line plays a key role in the induction of granulocytic differentiation mediated by all-trans retinoic acid [J].
Bertolaso, L ;
Gibellini, D ;
Secchiero, P ;
Previati, M ;
Falgione, D ;
Visani, G ;
Rizzoli, R ;
Capitani, S ;
Zauli, G .
BRITISH JOURNAL OF HAEMATOLOGY, 1998, 100 (03) :541-549
[7]   Phosphatidylinositol-3-kinase activation and atypical protein kinase C ζ phosphorylation characterize the DMSO signalling in erythroleukemia cells [J].
Cataldi, A ;
Di Pietro, R ;
Centurione, L ;
Grilli, A ;
Cutroneo, G ;
Miscia, S .
CELLULAR SIGNALLING, 2000, 12 (9-10) :667-672
[8]  
CROSSLEY M, 1994, J BIOL CHEM, V269, P16589
[9]   Analysis of the thrombopoietin receptor (MPL) promoter implicates GATA and Ets proteins in the coregulation of megakaryocyte-specific genes [J].
Deveaux, S ;
Filipe, A ;
Lemarchandel, V ;
Ghysdael, J ;
Romeo, PH ;
Mignotte, V .
BLOOD, 1996, 87 (11) :4678-4685
[10]   The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C [J].
DiazMeco, MT ;
Municio, MM ;
Frutos, S ;
Sanchez, P ;
Lozano, J ;
Sanz, L ;
Moscat, J .
CELL, 1996, 86 (05) :777-786