Reference - Detail
| RRC ID | 45883 |
|---|---|
| Author | Wilkinson DS, Jariwala JS, Anderson E, Mitra K, Meisenhelder J, Chang JT, Ideker T, Hunter T, Nizet V, Dillin A, Hansen M. |
| Title | Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy. |
| Journal | Mol Cell |
| Abstract |
The protein LC3 is indispensible for the cellular recycling process of autophagy and plays critical roles during cargo recruitment, autophagosome biogenesis, and completion. Here, we report that LC3 is phosphorylated at threonine 50 (Thr(50)) by the mammalian Sterile-20 kinases STK3 and STK4. Loss of phosphorylation at this site blocks autophagy by impairing fusion of autophagosomes with lysosomes, and compromises the ability of cells to clear intracellular bacteria, an established cargo for autophagy. Strikingly, mutation of LC3 mimicking constitutive phosphorylation at Thr(50) reverses the autophagy block in STK3/STK4-deficient cells and restores their capacity to clear bacteria. Loss of STK3/STK4 impairs autophagy in diverse species, indicating that these kinases are conserved autophagy regulators. We conclude that phosphorylation of LC3 by STK3/STK4 is an essential step in the autophagy process. Since several pathological conditions, including bacterial infections, display aberrant autophagy, we propose that pharmacological agents targeting this regulatory circuit hold therapeutic potential. |
| Volume | 57(1) |
| Pages | 55-68 |
| Published | 2015-1-8 |
| DOI | 10.1016/j.molcel.2014.11.019 |
| PII | S1097-2765(14)00914-9 |
| PMID | 25544559 |
| PMC | PMC4373083 |
| MeSH | Animals Autophagy / genetics* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Cells, Cultured Embryo, Mammalian Fibroblasts / metabolism* Fibroblasts / microbiology Gene Expression Regulation Humans Lysosomes / metabolism Membrane Fusion Mice Mice, Knockout Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism* Mutation Peptide Fragments / chemistry Phagosomes / metabolism Phosphorylation Protein Serine-Threonine Kinases / deficiency Protein Serine-Threonine Kinases / genetics* Serine-Threonine Kinase 3 Signal Transduction Streptococcus pyogenes / pathogenicity Streptococcus pyogenes / physiology Threonine / metabolism |
| IF | 15.584 |
| Times Cited | 83 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1900 |