Diet-Dependent Effects of the Drosophila Mnk1/Mnk2 Homolog Lk6 on Growth via eIF4E
| Autor: | Hugo Stocker, Kathrin T. Doepfner, Ernst Hafen, Jan H. Reiling |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Male p38 mitogen-activated protein kinases Molecular Sequence Data Gene Expression Biology Models Biological General Biochemistry Genetics and Molecular Biology Initiation factor Animals Drosophila Proteins Wings Animal Body Weights and Measures Amino Acid Sequence Amino Acids Phosphorylation Mitogen-Activated Protein Kinase Kinases eIF2 Agricultural and Biological Sciences(all) Kinase Biochemistry Genetics and Molecular Biology(all) EIF4E EIF4A1 Diet EIF4EBP1 Mutagenesis Insertional Oxidative Stress Eukaryotic Initiation Factor-4E Biochemistry Protein Biosynthesis Drosophila Female General Agricultural and Biological Sciences Sequence Alignment |
| Zdroj: | Current Biology. 15(13) |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2005.06.054 |
| Popis: | The control of cellular growth is tightly linked to the regulation of protein synthesis. A key function in translation initiation is fulfilled by the 5′ cap binding eukaryotic initiation factor 4E (eIF4E), and dysregulation of eIF4E is associated with malignant transformation and tumorigenesis [1, 2]. In mammals, the activity of eIF4E is modulated by phosphorylation at Ser209 by mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1 and Mnk2) [3–5], which themselves are activated by ERK and p38 MAPK in response to mitogens, cytokines or cellular stress [6]. Whether phosphorylation of eIF4E at Ser209 exerts a positive or inhibitory effect on translation efficiency has remained controversial. Here we provide a genetic characterization of the Drosophila homolog of Mnk1/2, Lk6. Lk6 function is dispensable under a high protein diet, consistent with the recent finding that mice lacking both Mnk1 and Mnk2 are not growth-impaired [4]. Interestingly, loss of Lk6 function causes a significant growth reduction when the amino acid content in the diet is reduced. Overexpression of Lk6 also results in growth inhibition in an eIF4E-dependent manner. We propose a model of eIF4E regulation that may reconcile the contradictory findings with regard to the role of phosphorylation by Mnk1/2. |
| Databáze: | OpenAIRE |
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