Gene interactions and pathways from curated databases and text-mining
EMBO J 2000, PMID: 10698949

Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation.

Kumar, V; Pandey, P; Sabatini, D; Kumar, M; Majumder, P K; Bharti, A; Carmichael, G; Kufe, D; Kharbanda, S

Hormones and growth factors induce protein translation in part by phosphorylation of the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). The rapamycin and FK506-binding protein (FKBP)-target 1 (RAFT1, also known as FRAP) is a mammalian homolog of the Saccharomyces cerevisiae target of rapamycin proteins (mTOR) that regulates 4E-BP1. However, the molecular mechanisms involved in growth factor-initiated phosphorylation of 4E-BP1 are not well understood. Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1. PKCdelta-mediated phosphorylation of 4E-BP1 is wortmannin resistant but rapamycin sensitive. As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation. Moreover, a dominant-negative mutant of PKCdelta inhibits serum-induced phosphorylation of 4E-BP1. These findings demonstrate that PKCdelta associates with RAFT1 and thereby regulates phosphorylation of 4E-BP1 and cap-dependent initiation of protein translation.

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Text Mining Data

eIF4E ⊣ 4E-BP1: " As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap dependent translation "

Manually curated Databases

  • IRef Biogrid Interaction: PRKCD — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4EBP1 — EIF4E (physical association, affinity chromatography technology)
  • IRef Innatedb Interaction: PRKCD — MTOR (unknown, -)
In total, 2 gene pairs are associated to this article in curated databases