RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24801387http://www.w3.org/2000/01/rdf-schema#comment"The present project was designed to investigate phosphorylation of p70S6K1 in an animal model of skeletal muscle overload. Within 24 h of male Sprague-Dawley rats undergoing unilateral tenotomy to induce functional overloading of the plantaris muscle, phosphorylation of the Thr³⁸⁹ and Thr⁴²¹/Ser⁴²⁴ sites on p70S6K1 was significantly elevated. Since the Thr⁴²¹/Ser⁴²⁴ sites are purportedly mammalian target of rapamycin complex 1 (mTORC1) independent, we sought to identify the kinase(s) responsible for their phosphorylation. Initially, we used IGF-I treatment of serum-deprived HEK-293E cells as an in vitro model system, because IGF-I promotes phosphorylation of p70S6K1 on both the Thr³⁸⁹ and Thr⁴²¹/Ser⁴²⁴ sites in skeletal muscle and in cells in culture. We found that, whereas the mTOR inhibitor TORIN2 prevented the IGF-I-induced phosphorylation of the Thr⁴²¹/Ser⁴²⁴ sites, it surprisingly enhanced phosphorylation of these sites during serum deprivation. JNK inhibition with SP600125 attenuated phosphorylation of the Thr⁴²¹/Ser⁴²⁴ sites, and in combination with TORIN2 both the effect of IGF-I and the enhanced Thr⁴²¹/Ser⁴²⁴ phosphorylation during serum deprivation were ablated. In contrast, both JNK activation with anisomycin and knockdown of the mTORC2 subunit rictor specifically stimulated phosphorylation of the Thr⁴²¹/Ser⁴²⁴ sites, suggesting that mTORC2 represses JNK-mediated phosphorylation of these sites. The role of JNK in mediating p70S6K1 phosphorylation was confirmed in the animal model noted above, where rats treated with SP600125 exhibited attenuated Thr⁴²¹/Ser⁴²⁴ phosphorylation. Overall, the results provide evidence that the mTORC1 and JNK signaling pathways coordinate the site-specific phosphorylation of p70S6K1. They also identify a novel role for mTORC1 and mTORC2 in the inhibition of JNK."xsd:string
http://purl.uniprot.org/citations/24801387http://purl.org/dc/terms/identifier"doi:10.1152/ajpendo.00064.2014"xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/author"Martin T.D."xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/author"Dennis M.D."xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/author"Jefferson L.S."xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/author"Kimball S.R."xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/author"Gordon B.S."xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/name"Am J Physiol Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/pages"E1397-405"xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/title"mTORC1 and JNK coordinate phosphorylation of the p70S6K1 autoinhibitory domain in skeletal muscle following functional overloading."xsd:string
http://purl.uniprot.org/citations/24801387http://purl.uniprot.org/core/volume"306"xsd:string
http://purl.uniprot.org/citations/24801387http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24801387
http://purl.uniprot.org/citations/24801387http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24801387
http://purl.uniprot.org/uniprot/#_A0A1L1WKJ1-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_A6IU70-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_A6KFU2-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_A6KFU3-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_A6KFU4-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_A6KFU5-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_A9LRT4-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_P49185-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_Q3U182-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387
http://purl.uniprot.org/uniprot/#_P42346-mappedCitation-24801387http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24801387