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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining
Cancer Cell 2004, PMID: 15261145

The LKB1 tumor suppressor negatively regulates mTOR signaling.

Shaw, Reuben J; Bardeesy, Nabeel; Manning, Brendan D; Lopez, Lyle; Kosmatka, Monica; DePinho, Ronald A; Cantley, Lewis C

Germline mutations in LKB1, TSC2, or PTEN tumor suppressor genes result in hamartomatous syndromes with shared tumor biological features. The recent observations of LKB1-mediated activation of AMP-activated protein kinase (AMPK) and AMPK inhibition of mTOR through TSC2 prompted us to examine the biochemical and biological relationship between LKB1 and mTOR regulation. Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2-dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR. These findings position aberrant mTOR activation at the nexus of these germline neoplastic conditions and suggest the use of mTOR inhibitors in the treatment of Peutz-Jeghers syndrome.

Diseases/Pathways annotated by Medline MESH: Colonic Polyps, Hamartoma, Peutz-Jeghers Syndrome, Tuberous Sclerosis
Document information provided by NCBI PubMed

Text Mining Data

AMP activated protein kinase (AMPK) → LKB1: " The recent observations of LKB1 mediated activation of AMP activated protein kinase (AMPK) and AMPK inhibition of mTOR through TSC2 prompted us to examine the biochemical and biological relationship between LKB1 and mTOR regulation "

mTOR ⊣ LKB1: " Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2 dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR "

LKB1 — TSC2: " Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2 dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR "

mTOR — TSC2: " Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2 dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR "

Manually curated Databases

  • IRef Biogrid Interaction: PRKAA1 — TSC2 (direct interaction, pull down)
  • NCI Pathway Database LKB1 signaling events: 14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB) → mTORC1 complex complex (MTOR-MLST8-RPTOR-AKT1S1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database LKB1 signaling events: 14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB) → mTORC1 complex/14-3-3 family complex (MTOR-MLST8-RPTOR-AKT1S1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database LKB1 signaling events: mTORC1 complex complex (MTOR-MLST8-RPTOR-AKT1S1) → mTORC1 complex/14-3-3 family complex (MTOR-MLST8-RPTOR-AKT1S1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 67 gene pairs are associated to this article in curated databases