Distinct signalling pathways mediate insulin and phorbol ester- stimulated eukaryotic initiation factor 4F assembly and protein synthesis in HEK 293 cells

Herbert, T. P. and Kilhams, G. R. and Batty, I. H. and Proud, C. G. (2000) Distinct signalling pathways mediate insulin and phorbol ester- stimulated eukaryotic initiation factor 4F assembly and protein synthesis in HEK 293 cells. Journal of Biological Chemistry, 275 (15). pp. 11249-11256. ISSN 0021-9258

Full content URL: https://doi.org/10.1074/jbc.275.15.11249

Documents
28238 J. Biol. Chem.-2000-Herbert-11249-56.pdf
[img]
[Download]
[img]
Preview
PDF
28238 J. Biol. Chem.-2000-Herbert-11249-56.pdf - Whole Document

404kB
Item Type:Article
Item Status:Live Archive

Abstract

Stimulation of serum-starved human embryonic kidney (HEK) 293 cells with either the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), or insulin resulted in increases in the phosphorylation of 4E-BP1 and p70 S6 kinase, eIF4F assembly, and protein synthesis. All these effects were blocked by rapamycin, a specific inhibitor of mTOR. Phosphatidylinositol 3-kinase and protein kinase B were activated by insulin but not by TPA. Therefore TPA can induce eIF4F assembly, protein synthesis, and the phosphorylation of p70 S6 kinase and 4E-BP1 independently of both phosphatidylinositol 3-kinase and protein kinase B. Using two structurally unrelated inhibitors of MEK (PD098059 and U0126), we provide evidence that Erk activation is important in TPA stimulation of eIF4F assembly and the phosphorylation of p70 S6 kinase and 4E-BP1 and that basal MEK activity is important for basal, insulin, and TPA-stimulated protein synthesis. Transient transfection of constitutively active mitogen-activated protein kinase interacting kinase 1 (the eIF4E kinase) indicated that inhibition of protein synthesis and eIF4F assembly by PD098059 is not through inhibition of eIF4E phosphorylation but of other signals emanating from MEK. This report also provides evidence that increased eIF4E phosphorylation alone does not affect the assembly of the eIF4F complex or general protein synthesis.

Keywords:Diabetes
Subjects:F Physical Sciences > F165 Biomolecular Chemistry
Divisions:College of Science > School of Pharmacy
Related URLs:
ID Code:28238
Deposited On:16 Mar 2018 16:53

Repository Staff Only: item control page