Drosophila Lk6 kinase controls phosphorylation of eukaryotic translation initiation factor 4E and promotes normal growth and development.
Eukaryotic initiation factor 4E (eIF4E) controls a crucial step of translation initiation and is critical for cell growth . Biochemical studies have shown that it undergoes a regulated phosphorylation by the MAP-kinase signal-integrating kinases Mnk1 and Mnk2 . Although the role of eIF4E phosphorylation in mammalian cells has remained elusive , recent work in Drosophila has established that it is required for growth and development . Here, we demonstrate that a previously identified Drosophila kinase called Lk6 is the functional homolog of mammalian Mnk kinases. We generated lk6 loss-of-function alleles and found that eIF4E phosphorylation is dramatically reduced in lk6 mutants. Importantly, lk6 mutants exhibit reduced viability, slower development, and reduced adult size, demonstrating that Lk6 function is required for organismal growth. Moreover, we show that uniform lk6 expression rescues the lethality of eIF4E hypomorphic mutants in an eIF4E phosphorylation site-dependent manner and that the two proteins participate in a common complex in Drosophila S2 cells, confirming the functional link between Lk6 and eIF4E. This work demonstrates that Lk6 exerts a tight control on eIF4E phosphorylation and is necessary for normal growth and development.
Arquier
Nathalie
N
Institute for Signalling, Developmental Biology and Cancer, Centre National de la Recherche Scientifique Unité, Mixte de Recherche 6543, Parc Valrose, 06108 Nice Cedex 2, France.
Bourouis
Marc
M
Colombani
Julien
J
Léopold
Pierre
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001837:Body Weights and Measures; D002478:Cells, Cultured; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development*; D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D047468:Immunoprecipitation; D007814:Larva / Q000254:growth & development; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010053:Ovary / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014162:Transfection
D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; C500415:Lk6 protein, Drosophila; D020929:Mitogen-Activated Protein Kinase Kinases