Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The LKB1 tumour suppressor kinase phosphorylates and activates a number of protein kinases belonging to the AMP-activated protein kinase (AMPK) subfamily. We have used a modified tandem affinity purification strategy to identify proteins that interact with AMPKalpha, as well as the twelve AMPK-related kinases that are activated by LKB1. The AMPKbeta and AMPKgamma regulatory subunits were associated with AMPKalpha, but not with any of the AMPK-related kinases, explaining why AMP does not influence the activity of these enzymes. In addition, we identified novel binding partners that interacted with one or more of the AMPK subfamily enzymes, including fat facets/ubiquitin specific protease-9 (USP9), AAA-ATPase-p97, adenine nucleotide translocase, protein phosphatase 2A holoenzyme and isoforms of the phospho-protein binding adaptor 14-3-3. Interestingly, the 14-3-3 isoforms bound directly to the T-loop Thr residue of QSK and SIK, after these were phosphorylated by LKB1. Consistent with this, the 14-3-3 isoforms failed to interact with non-phosphorylated QSK and SIK, in LKB1 knockout muscle or in HeLa cells in which LKB1 is not expressed. Moreover, mutation of the T-loop Thr phosphorylated by LKB1, prevented QSK and SIK from interacting with 14-3-3 in vitro. Binding of 14-3-3 to QSK and SIK, enhanced catalytic activity towards the TORC2 protein and the AMARA peptide, and was required for the cytoplasmic localization of SIK and for localization of QSK to punctate structures within the cytoplasm. To our knowledge, this study provides the first example of 14-3-3 binding directly to the T-loop of a protein kinase and influencing its catalytic activity and cellular localization.
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PMID:14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK. 1630 28

More than 200 plants have been suffering from Verticillium wilt caused by Verticillium dahliae (V. dahliae) across the world. The target of rapamycin (TOR) is a lethal gene and controls cell growth and development in various eukaryotes, but little is known about TOR signaling in V. dahliae. Here, we found that V. dahliae strain is hypersensitive to rapamycin in the presence of rapamycin binding protein VdFKBP12 while the deletion mutant aaavdfkbp12 is insensitive to rapamycin. Heterologous expressing VdFKBP12 in Arabidopsis conferred rapamycin sensitivity, indicating that VdFKBP12 can bridge the interaction between rapamycin and TOR across species. The key across species of TOR complex 1 (TORC1) and TORC2 have been identified in V. dahliae, suggesting that TOR signaling pathway is evolutionarily conserved in eukaryotic species. Furthermore, the RNA-seq analysis showed that ribosomal biogenesis, RNA polymerase II transcription factors and many metabolic processes were significantly suppressed in rapamycin treated cells of V. dahliae. Importantly, transcript levels of genes associated with cell wall degrading enzymes (CWEDs) were dramatically down-regulated in TOR-inhibited cells. Further infection assay showed that the pathogenicity of V. dahliae and occurrence of Verticillium wilt can be blocked in the presence of rapamycin. These observations suggested that VdTOR is a key target of V. dahliae for controlling and preventing Verticillium wilt in plants.
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PMID:Functional Characterization of Target of Rapamycin Signaling in Verticillium dahliae. 3091 4