| http://purl.uniprot.org/citations/14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14985505 | http://www.w3.org/2000/01/rdf-schema#comment | "AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status found in all eukaryotic cells. AMPK is activated by stimuli that increase the cellular AMP/ATP ratio. Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive. Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of AMPK activation in several mammalian cell types. We show that LKB1 directly phosphorylates Thr-172 of AMPKalpha in vitro and activates its kinase activity. LKB1-deficient murine embryonic fibroblasts show nearly complete loss of Thr-172 phosphorylation and downstream AMPK signaling in response to a variety of stimuli that activate AMPK. Reintroduction of WT, but not kinase-dead, LKB1 into these cells restores AMPK activity. Furthermore, we show that LKB1 plays a biologically significant role in this pathway, because LKB1-deficient cells are hypersensitive to apoptosis induced by energy stress. On the basis of these results, we propose a model to explain the apparent paradox that LKB1 is a tumor suppressor, yet cells lacking LKB1 are resistant to cell transformation by conventional oncogenes and are sensitive to killing in response to agents that elevate AMP. The role of LKB1/AMPK in the survival of a subset of genetically defined tumor cells may provide opportunities for cancer therapeutics."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0308061100"xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/author | "Cantley L.C."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/author | "Witters L.A."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/author | "Bardeesy N."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/author | "Hurley R.L."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/author | "Shaw R.J."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/author | "DePinho R.A."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/author | "Kosmatka M."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/pages | "3329-3335"xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/title | "The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress."xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://purl.uniprot.org/core/volume | "101"xsd:string |
| http://purl.uniprot.org/citations/14985505 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/14985505 |
| http://purl.uniprot.org/citations/14985505 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/14985505 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YVX0-mappedCitation-14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14985505 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YX03-mappedCitation-14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14985505 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YY63-mappedCitation-14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14985505 |
| http://purl.uniprot.org/uniprot/#_D3Z783-mappedCitation-14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14985505 |
| http://purl.uniprot.org/uniprot/#_D3YYP9-mappedCitation-14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14985505 |
| http://purl.uniprot.org/uniprot/#_D3Z1Z4-mappedCitation-14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14985505 |
| http://purl.uniprot.org/uniprot/#_D4P556-mappedCitation-14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14985505 |
| http://purl.uniprot.org/uniprot/#_D3YXX3-mappedCitation-14985505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/14985505 |