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Functional interaction between RAFT1/FRAP/mTOR and protein kinase Cδ in the regulation of cap‐dependent initiation of translation
Author(s) -
Kumar Vijay,
Pandey Pramod,
Sabatini David,
Kumar Madhur,
Majumder Pradip K.,
Bharti Ajit,
Carmichael Gordon,
Kufe Donald,
Kharbanda Surender
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.5.1087
Subject(s) - biology , translation (biology) , microbiology and biotechnology , pi3k/akt/mtor pathway , eukaryotic translation , eif2 , kinase , computational biology , biochemistry , signal transduction , messenger rna , gene
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 Cδ (PKCδ) associates with RAFT1 and that PKCδ is required for the phosphorylation and inactivation of 4E‐BP1. PKCδ‐mediated phosphorylation of 4E‐BP1 is wortmannin resistant but rapamycin sensitive. As shown for serum, phosphorylation of 4E‐BP1 by PKCδ inhibits the interaction between 4E‐BP1 and eIF4E and stimulates cap‐dependent translation. Moreover, a dominant‐negative mutant of PKCδ inhibits serum‐induced phosphorylation of 4E‐BP1. These findings demonstrate that PKCδ associates with RAFT1 and thereby regulates phosphorylation of 4E–BP1 and cap‐dependent initiation of protein translation.