Energy-dependent regulation of cell structure by AMP-activated protein kinase
| Autor: | Soo-Young Lee, Jin Man Kim, Minho Shong, Hyongjong Koh, Yongsung Kim, Jun Hee Lee, Roger E. Karess, Sang-Hee Lee, Myung Jin Kim, Jongkyeong Chung, Jaeseob Kim |
|---|---|
| Přispěvatelé: | Chungnam National Univesity School of Medicine, Taejon, Korea, Chungnam National Univesity School of Medicine, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
AMP-Activated Protein Kinases MESH: Multienzyme Complexes 0302 clinical medicine AMP-Activated Protein Kinase Kinases AMP-activated protein kinase Cell polarity Drosophila Proteins MESH: Animals Phosphorylation 0303 health sciences Multidisciplinary biology Kinase MESH: Energy Metabolism Cell Polarity MESH: Myosin Light Chains Cell biology Drosophila melanogaster Phenotype 030220 oncology & carcinogenesis Female MESH: Cell Polarity Myosin Light Chains Myosin light-chain kinase MESH: Drosophila Proteins Mitosis [SDV.BC]Life Sciences [q-bio]/Cellular Biology Protein Serine-Threonine Kinases MESH: Phenotype MESH: Protein-Serine-Threonine Kinases Cell Line MESH: Drosophila melanogaster 03 medical and health sciences Multienzyme Complexes Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Protein kinase A MESH: Protein Kinases 030304 developmental biology MESH: Humans MESH: Phosphorylation AMPK MESH: Mitosis MESH: Male MESH: Cell Line biology.protein Energy Metabolism Protein Kinases MESH: Female Cytokinesis |
| Zdroj: | Nature Nature, Nature Publishing Group, 2007, 447 (7147), pp.1017-20. ⟨10.1038/nature05828⟩ |
| ISSN: | 0028-0836 1476-4679 |
| DOI: | 10.1038/nature05828⟩ |
| Popis: | AMP-activated protein kinase (AMPK, also known as SNF1A) has been primarily studied as a metabolic regulator that is activated in response to energy deprivation. Although there is relatively ample information on the biochemical characteristics of AMPK, not enough data exist on the in vivo function of the kinase. Here, using the Drosophila model system, we generated the first animal model with no AMPK activity and discovered physiological functions of the kinase. Surprisingly, AMPK-null mutants were lethal with severe abnormalities in cell polarity and mitosis, similar to those of lkb1-null mutants. Constitutive activation of AMPK restored many of the phenotypes of lkb1-null mutants, suggesting that AMPK mediates the polarity- and mitosis-controlling functions of the LKB1 serine/threonine kinase. Interestingly, the regulatory site of non-muscle myosin regulatory light chain (MRLC; also known as MLC2) was directly phosphorylated by AMPK. Moreover, the phosphomimetic mutant of MRLC rescued the AMPK-null defects in cell polarity and mitosis, suggesting MRLC is a critical downstream target of AMPK. Furthermore, the activation of AMPK by energy deprivation was sufficient to cause dramatic changes in cell shape, inducing complete polarization and brush border formation in the human LS174T cell line, through the phosphorylation of MRLC. Taken together, our results demonstrate that AMPK has highly conserved roles across metazoan species not only in the control of metabolism, but also in the regulation of cellular structures. |
| Databáze: | OpenAIRE |
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