Gene interactions and pathways from curated databases and text-mining
Kidney Int 2001, PMID: 11231341

Insulin regulation of protein translation repressor 4E-BP1, an eIF4E-binding protein, in renal epithelial cells.

Bhandari, B K; Feliers, D; Duraisamy, S; Stewart, J L; Gingras, A C; Abboud, H E; Choudhury, G G; Sonenberg, N; Kasinath, B S

BACKGROUND

Augmented protein translation by insulin involves activation of eukaryotic initiation factor 4E (eIF4E) that follows release of eIF4E from a heterodimeric complex by phosphorylation of its inhibitory binding protein, 4E-BP1. We examined insulin regulation of 4E-BP1 phosphorylation in murine proximal tubular epithelial cells.

RESULTS

Insulin (1 nmol/L) increased de novo protein synthesis by 58 +/- 11% (P < 0.001). Insulin also augmented 4E-BP1 phosphorylation and phosphatidylinositol 3-kinase (PI 3-kinase) activity in antiphosphotyrosine immunoprecipitates. This could be prevented by PI 3-kinase inhibitors, Wortmannin, and LY294002. Insulin also activated Akt that lies downstream of PI 3-kinase. Rapamycin abrogated 4E-BP1 phosphorylation in response to insulin, suggesting involvement of mammalian target of rapamycin (mTOR), a kinase downstream of Akt. Insulin-stimulated phosphorylation of 4E-BP1 was also inhibited by PD098059, implying involvement of Erk-1/-2 mitogen-activated protein (MAP) kinase. An increase in Erk-1/-2 type MAP kinase activity by insulin was directly confirmed in an immunokinase assay and was found to be PI 3-kinase dependent.

CONCLUSIONS

In proximal tubular epithelial cells, insulin augments 4E-BP1 phosphorylation, which is PI 3-kinase and mTOR dependent. The requirement for Erk-1/-2 MAP kinase activation for 4E-BP1 phosphorylation by insulin suggests a cross-talk between PI 3-kinase and Erk-1/-2-type MAP kinase pathways.

Document information provided by NCBI PubMed

Text Mining Data

4E-BP1 — Insulin: " Insulin regulation of protein translation repressor 4E-BP1 , an eIF4E binding protein, in renal epithelial cells "

4E-BP1 — insulin: " We examined insulin regulation of 4E-BP1 phosphorylation in murine proximal tubular epithelial cells "

4E-BP1 → Insulin: " Insulin also augmented 4E-BP1 phosphorylation and phosphatidylinositol 3-kinase ( PI 3-kinase ) activity in antiphosphotyrosine immunoprecipitates "

Akt → Insulin: " Insulin also activated Akt that lies downstream of PI 3-kinase "

4E-BP1 → insulin: " Rapamycin abrogated 4E-BP1 phosphorylation in response to insulin , suggesting involvement of mammalian target of rapamycin (mTOR), a kinase downstream of Akt "

4E-BP1 → Insulin: " Insulin stimulated phosphorylation of 4E-BP1 was also inhibited by PD098059, implying involvement of Erk-1/-2 mitogen activated protein ( MAP ) kinase "

4E-BP1 → Erk-1/-2: " The requirement for Erk-1/-2 MAP kinase activation for 4E-BP1 phosphorylation by insulin suggests a cross-talk between PI 3-kinase and Erk-1/-2-type MAP kinase pathways "

4E-BP1 → Erk-1/-2: " The requirement for Erk-1/-2 MAP kinase activation for 4E-BP1 phosphorylation by insulin suggests a cross-talk between PI 3-kinase and Erk-1/-2-type MAP kinase pathways "

Manually curated Databases

No curated data.