Reference: Kimpe M, et al. (2012) Pkh1 interacts with and phosphorylates components of the yeast Gcn2/eIF2α system. Biochem Biophys Res Commun 419(1):89-94

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Abstract


The yeast Saccharomyces cerevisiae responds to amino acid deprivation by increasing translation of the transcription factor Gcn4, which enhances expression of amino acid biosynthetic genes. Accumulation of uncharged tRNAs activates the Gcn2 protein kinase, which phosphorylates the alpha subunit of the eukaryotic initiation factor 2 (eIF2α). The resulting downregulation of eIF2 activity causes reduction of general translation and stimulation of GCN4 translation. S. cerevisiae contains three PDK1 orthologs (encoded by PKH1, PKH2 and PKH3) that have been implicated in nutrient signaling. Using heterologously expressed proteins, we demonstrate physical interaction between Pkh1 and all three subunits of eIF2 as well as Gcn2. We confirm the interaction between Pkh1 and Gcn2 by co-immunoprecipitation in yeast cell extracts and show that Pkh1 can phosphorylate Gcn2 in vitro. However, Pkh1 inactivation did not affect eIF2α-S51 phosphorylation in vivo or GCN4 translation in response to amino acid deprivation. Hence, the physiological importance of the close interactions between Pkh1 and Gcn2 or eIF2 could depend on other conditions and/or other targets of the Gcn2/eIF2 system.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Kimpe M, Voordeckers K, Thevelein JM, Van Zeebroeck G
Primary Lit For
SUI2 | GCN2 | PKH1 | Eukaryotic translation initiation factor 2 complex
Additional Lit For
GCD11 | SCH9 | TPK1 | SUI3

Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 17 entries for 7 genes

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InteractorInteractorAssayAnnotationActionModification
GCD11PKH1Reconstituted Complexmanually curatedBait-HitNo Modification
GCD11SCH9Reconstituted Complexmanually curatedBait-HitNo Modification
GCD11TPK1Reconstituted Complexmanually curatedHit-BaitNo Modification
GCD11PKH1Reconstituted Complexmanually curatedHit-BaitNo Modification
GCD11SCH9Reconstituted Complexmanually curatedHit-BaitNo Modification
GCN2PKH1Reconstituted Complexmanually curatedBait-HitNo Modification
GCN2PKH1Reconstituted Complexmanually curatedHit-BaitNo Modification
GCN2PKH1Affinity Capture-Westernmanually curatedHit-BaitNo Modification
GCN2PKH1Biochemical Activitymanually curatedHit-Baitphosphorylated residue
PKH1SUI2Reconstituted Complexmanually curatedHit-BaitNo Modification
Showing 1 to 10 of 17 entries