| http://purl.uniprot.org/citations/27994061 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27994061 | http://www.w3.org/2000/01/rdf-schema#comment | "Autophagy is an evolutionarily conserved intracellular degradation/recycling system that is essential for cellular homeostasis but is dysregulated in a number of diseases, including myocardial hypertrophy. Although it is clear that limiting or accelerating autophagic flux can result in pathological cardiac remodeling, the physiological signaling pathways that fine-tune cardiac autophagy are poorly understood. Herein, we demonstrated that stimulation of cardiomyocytes with phenylephrine (PE), a well known hypertrophic agonist, suppresses autophagy and that activation of focal adhesion kinase (FAK) is necessary for PE-stimulated autophagy suppression and subsequent initiation of hypertrophic growth. Mechanistically, we showed that FAK phosphorylates Beclin1, a core autophagy protein, on Tyr-233 and that this post-translational modification limits Beclin1 association with Atg14L and reduces Beclin1-dependent autophagosome formation. Remarkably, although ectopic expression of wild-type Beclin1 promoted cardiomyocyte atrophy, expression of a Y233E phosphomimetic variant of Beclin1 failed to affect cardiomyocyte size. Moreover, genetic depletion of Beclin1 attenuated PE-mediated/FAK-dependent initiation of myocyte hypertrophy in vivo Collectively, these findings identify FAK as a novel negative regulator of Beclin1-mediated autophagy and indicate that this pathway can facilitate the promotion of compensatory hypertrophic growth. This novel mechanism to limit Beclin1 activity has important implications for treating a variety of pathologies associated with altered autophagic flux."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m116.758268"xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/author | "Cheng Z."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/author | "Zhu Q."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/author | "Taylor J.M."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/author | "Cyr D.M."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/author | "Mack C.P."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/author | "Dee R."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/author | "Opheim Z."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/pages | "2065-2079"xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/title | "Focal Adhesion Kinase-mediated Phosphorylation of Beclin1 Protein Suppresses Cardiomyocyte Autophagy and Initiates Hypertrophic Growth."xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://purl.uniprot.org/core/volume | "292"xsd:string |
| http://purl.uniprot.org/citations/27994061 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27994061 |
| http://purl.uniprot.org/citations/27994061 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27994061 |
| http://purl.uniprot.org/uniprot/P97718#attribution-37AD56B189FE1AA3D221FF792B952576 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27994061 |
| http://purl.uniprot.org/uniprot/O88597#attribution-4FF981DFE3ADE1D87987F1B66BCE1A5B | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27994061 |
| http://purl.uniprot.org/uniprot/O88597#attribution-C5D9ABFCCA3D6969EA400DE7264BD071 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27994061 |
| http://purl.uniprot.org/uniprot/P34152#attribution-37AD56B189FE1AA3D221FF792B952576 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27994061 |
| http://purl.uniprot.org/uniprot/Q91VR7#attribution-37AD56B189FE1AA3D221FF792B952576 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27994061 |
| http://purl.uniprot.org/uniprot/P05480#attribution-37AD56B189FE1AA3D221FF792B952576 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27994061 |
| http://purl.uniprot.org/uniprot/#_E9QAM0-mappedCitation-27994061 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27994061 |
| http://purl.uniprot.org/uniprot/#_A0A140LHA4-mappedCitation-27994061 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27994061 |