SIGNALING 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

Initiation factor (eIF) 4E plays a key role in the regulation of trans lation, Its activity is modulated both by phosphorylation and by its a ssociation with an inhibitory protein, 4E-BP1, which precludes its int eraction with eIF4G. Although increased eIF4E phosphorylation has been correlated with the activation of protein synthesis in T cells, the k inase(s) and/or phosphatase(s) involved have not been characterised, T here is evidence for phosphorylation of eIF4E mediated by both protein kinase C-dependent and -independent signalling pathways. In these stu dies, I show that activation of protein kinase C with phorbol ester, s timulation via the T cell receptor complex with the monoclonal antibod y OKT3 and cellular stresses increase the phosphorylation of eIF4E in Jurkat T cells. In contrast to published data, inhibition of either th e ERK MAP kinase or p38 MAP kinase signalling pathways does not affect the PMA- or OKT3-stimulated increase in eIF4E phosphorylation. Howeve r, simultaneous inhibition of both of these pathways with selective in hibitors is required to completely abrogate the enhanced phosphorylati on of eIF4E. These data show that in Jurkat cells, protein kinase C mo dulates the phosphorylation status of eIF4E indirectly via the ERK and /or p38 MAP kinase signalling pathways. (C) 1997 Federation of Europea n Biochemical Societies.