Analysis of the regulatory motifs in eukaryotic initiation factor 4E-binding protein 1

Simple item page
dc.contributor.authorLee, V.
dc.contributor.authorHealy, T.
dc.contributor.authorFonseca, B.
dc.contributor.authorHayashi, A.
dc.contributor.authorProud, C.
dc.date.issued2008
dc.description.abstractMammalian target of rapamycin complex 1 (mTORC1) phosphorylates proteins such as eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and the S6 kinases. These substrates contain short sequences, termed TOR signalling (TOS) motifs, which interact with the mTORC1 component raptor. Phosphorylation of 4E-BP1 requires an additional feature, termed the RAIP motif (Arg–Ala–Ile–Pro). We have analysed the interaction of 4E-BP1 with raptor and the amino acid residues required for functional RAIP and TOS motifs, as assessed by raptor binding and the phosphorylation of 4E-BP1 in human cells. Binding of 4E-BP1 to raptor strongly depends on an intact TOS motif, but the RAIP motif and additional C-terminal features of 4E-BP1 also contribute to this interaction. Mutational analysis of 4E-BP1 reveals that isoleucine is a key feature of the RAIP motif, that proline is also very important and that there is greater tolerance for substitution of the first two residues. Within the TOS motif, the first position (phenylalanine in the known motifs) is most critical, whereas a wider range of residues function in other positions (although an uncharged aliphatic residue is preferred at position three). These data provide important information on the structural requirements for efficient signalling downstream of mTORC1.
dc.description.statementofresponsibilityVivian H. Y. Lee, Timothy Healy, Bruno D. Fonseca, Amanda Hayashi and Christopher G. Proud
dc.identifier.citationThe Federation of European Biochemical Societies (FEBS) Journal, 2008; 275(9):2185-2199
dc.identifier.doi10.1111/j.1742-4658.2008.06372.x
dc.identifier.issn1742-464X
dc.identifier.issn1742-4658
dc.identifier.orcidProud, C. [0000-0003-0704-6442]
dc.identifier.urihttp://hdl.handle.net/2440/82645
dc.language.isoen
dc.publisherBlackwell Publishing Ltd
dc.rights© 2008 The Authors
dc.source.urihttps://doi.org/10.1111/j.1742-4658.2008.06372.x
dc.subject4E-BP1
dc.subjectmTOR
dc.subjectmTORC1
dc.subjectRAIP motif
dc.subjectTOS motif
dc.titleAnalysis of the regulatory motifs in eukaryotic initiation factor 4E-binding protein 1
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Molecular and Biomedical Science publications