Signalling through either the p38 or ERK mitogen‐activated protein (MAP) kinase pathway is obligatory for phorbol ester and T cell receptor complex (TCR‐CD3)‐stimulated phosphorylation of initiation factor (eIF) 4E in Jurkat T cells

FEBS Letters

Morley, Simon J¹ 

[1] Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK

关键词: Initiation factor;    eIF4E;    Mitogen-activated protein kinase;    eIF;    eukaryotic initiation factor;    m7GTP;    7-methylguanosine triphosphate;    SDS;    sodium dodecyl sulphate;    PMA;    phorbol 12-myristate 13-acetate;    PMSF;    phenylmethylsulphonyl fluoride;    PVDF;    polyvinylidene difluoride;    MOPS;    (3-[N-morpholino] propanesulfonic acid;    EGTA;    ethylene glycol-bis(β-aminoethyl ether);    PAGE;    polyacrylamide gel electrophoresis;    VSIEF;    vertical slab isoelectric focusing;    JNK/SAPK;    c-jun NH2-terminal kinase/stress-activated protein kinase;    MAP;    mitogen-activated protein;    4E-BP;    eIF4E binding protein;   

DOI  :  10.1016/S0014-5793(97)01405-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Initiation factor (eIF) 4E plays a key role in the regulation of translation. Its activity is modulated both by phosphorylation and by its association with an inhibitory protein, 4E-BP1, which precludes its interaction with eIF4G. Although increased eIF4E phosphorylation has been correlated with the activation of protein synthesis in T cells, the kinase(s) and/or phosphatase(s) involved have not been characterised. There is evidence for phosphorylation of eIF4E mediated by both protein kinase C-dependent and -independent signalling pathways. In these studies, I show that activation of protein kinase C with phorbol ester, stimulation via the T cell receptor complex with the monoclonal antibody OKT3 and cellular stresses increase the phosphorylation of eIF4E in Jurkat T cells. In contrast to published data, inhibition of either the ERK MAP kinase or p38 MAP kinase signalling pathways does not affect the PMA- or OKT3-stimulated increase in eIF4E phosphorylation. However, simultaneous inhibition of both of these pathways with selective inhibitors is required to completely abrogate the enhanced phosphorylation of eIF4E. These data show that in Jurkat cells, protein kinase C modulates the phosphorylation status of eIF4E indirectly via the ERK and/or p38 MAP kinase signalling pathways.

【 授权许可】

Unknown