ERK and p38 pathways regulate amino acid signalling
| Autor: | Eduard Casas-Terradellas, Ramon Bartrons, Irantzu Tato, Jose Luis Rosa, Francesc Ventura |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
p38 mitogen-activated protein kinases
Immunoblotting P70-S6 Kinase 1 p38 Ribosomal Protein S6 Kinases 90-kDa p38 Mitogen-Activated Protein Kinases MAP2K7 Phosphatidylinositol 3-Kinases Humans Immunoprecipitation MSK Protein phosphorylation Amino Acids Phosphorylation RNA Small Interfering Molecular Biology Cells Cultured MAPK14 Phosphoinositide-3 Kinase Inhibitors chemistry.chemical_classification Cell Nucleus Mitogen-Activated Protein Kinase 1 Sirolimus Antibiotics Antineoplastic Mitogen-Activated Protein Kinase 3 biology Kinase RSK Ribosomal Protein S6 Kinases 70-kDa Cell Biology S6K1 Cell biology Amino acid Androstadienes Protein Transport ERK Biochemistry chemistry Mitogen-activated protein kinase biology.protein Wortmannin Immunosuppressive Agents Plasmids Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. (12):2241-2254 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2008.08.011 |
| Popis: | The ribosomal protein S6 kinase 1 (S6K1) is emerging as a common downstream target of signalling by hormones and nutrients such as insulin and amino acids. Here, we have investigated how amino acids signal through the S6K1 pathway. First, we found that a commercial anti-phospho-Thr389-S6K1 antibody detects an 80–90 kDa protein that is rapidly phosphorylated in response to amino acids. Unexpectedly, this phosphorylation was insensitive to both mTOR and PI-3 kinase inhibitors, and knockdown experiments showed that this protein was not S6K1. Looking for candidate targets of this phosphorylation, we found that amino acids stimulated phosphorylation of RSK and MSK kinases at residues that are homologous to Thr389 in S6K1. In turn, these phosphorylations required the activity of either p38 or ERK MAP kinases, which could compensate for each other. Moreover, we show that these MAP kinases are also needed for the amino acid-induced phosphorylation of S6K1 at Thr421/Ser424, as well as for that of S6K1 substrate, the S6 ribosomal protein. Consistent with these results, concomitant inhibition of p38 and ERK pathways also antagonised the well-known effects of amino acids on the process of autophagy. Altogether, these findings demonstrate a previously unknown role for MAP kinases in amino acid signalling. |
| Databáze: | OpenAIRE |
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