Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 30 for “"LKB1"”.
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Novel Posttranslational Modification In Lkb1 Activation and Function
… involved in metabolism is Liver Kinase B1 (LKB1). LKB1 is the major upstream kinase of the evolutionarily conserved metabolic sensor—AMP-activated protein kinase (AMPK). Activation of the LKB1/AMPK pathway provides a survival advantage for cells under energy stress. LKB1 forms a …
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Regulation and role of the LKB1-AMPK pathway
… activation loop of the kinase domain, by either LKB1 or CaMKKß. Increases in Thr172 phosphorylation can be mediated by either protecting this site against dephosphorylation by protein phosphatases, or by promoting its phosphorylation by upstream kinases, both of which were proposed to be mediated …
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Understanding The Role of Sumoylation In Regulating Lkb1 Function
… during metabolic stress. Liver kinase B1 (LKB1), one of the key regulators of cellular energy balance, was initially discovered as a tumor suppressor mutated in patients with Peutz-Jeghers syndrome. Germline mutations in LKB1 predispose patients to develop several benign and malignant …
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Structure of the LKB1-STRAD-MO25 tumour suppressor complex
… ago established a link between mutations of the LKB1 gene and the Peutz-Jeghers cancer syndrome. Since then, much effort has been devoted to understanding the functional roles of the protein encoded by the LKB1 gene. LKB1 is a Ser/Thr kinase that is activated by binding to the pseudokinase STRAD …
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PKA as an Upstream Kinase for LKB1/STRAD/MO25
The LKB1/STRAD/MO25 complex (LSMK) has been identified as the major upstream kinase for AMP-activated protein kinase (AMPK). PKA phosphorylates LKB1 at the Ser428 residue in humans and Ser431 residue in mice. We investigated PKA as an upstream kinase for LSMK. LKB1 that had been incubated with PKA …
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LKB1, CCL2, and Macrophages: A New Axis of Endometrial Cancer Progression
… beyond the uterus. The serine-threonine kinase LKB1 has been identified as a potent suppressor of uterine cancer. Combined genetic, proteomic, and in vivo studies in genetically engineered mouse models show that loss of LKB1 protein is associated with high grade, high stage tumors with …
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LKB1 signaling pathways in adipocytes - Focus on the AMPK-related kinase SIK2
… been implicated in the regulation of metabolism. LKB1 is known as a tumor suppressor and was recently found to be required for the activity of AMPK and most of its related kinases, phosphorylating a specific threonine residue in their activation loop. The aim of this thesis was to investigate the …
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Lkb1 Deficient Non-Small Cell Lung Cancer Cells Are Vulnerable to Energy Stress Induced By Atp Depletion
… of lung cancer patients survive beyond 5 years. LKB1 is the third most mutated gene in lung cancer. It has been shown that LKB1 is mutated in at least 15% to 30% of NSCLC. Tumor with LKB1 mutation is associated with poor differentiation, high metastasis and worse response to chemotherapy. The …
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The Role of LKBI Tumor Suppressor in Endometrial Cancer
The LKB1 gene contributes to endometrial carcinogenesis in both the mouse and human. Although this role was not anticipated based on the tumor spectrum observed in Peutz Jegher women, many tumor suppressors have been found to have a much broader role in cancer than would have been predicted on the …
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Regulation of LKB1-STRAD-MO25 Complex Expression and Activation of AMPK in Skeletal Muscle by Thyroid Hormone
… is regulated by an upstream kinase (AMPKK). The LKB1-STRAD-MO25 complex is a major AMPKK in skeletal muscle. This experiment was designed to determine whether the increase in AMPK activity is accompanied by a thyroid hormone-induced increase in the expression of the LKB1-STRAD-MO25 complex. …
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The Effects of 3-Phosphoglycerate and Other Metabolites on the Activation of AMP-Activated Protein Kinase by LKB1/STRAD/MO25
… kinase (AMPK) by an upstream kinase, AMPKK. The LKB1-STRAD-MO25 complex is the major AMPKK in skeletal muscle; however, LKB1-STRAD-MO25 activity is not increased by muscle contraction. This relationship suggests that phosphorylation of AMPK by LKB1-STRAD-MO25 during skeletal muscle contraction …
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AXL Targeting Restores PD-1 Blockade Sensitivity of STK11/LKB1 Mutant NSCLC Through Expansion of TCF1+ CD8 T Cells
Mutations in STK11/LKB1 in non-small cell lung cancer (NSCLC) are associated with poor patient responses to immune checkpoint blockade (ICB) for unknown reasons. We found that introduction of a Stk11/Lkb1 (L) mutation into murine lung adenocarcinomas driven by mutant Kras and Trp53 (KP) resulted in …
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Targeting Glutamine Metabolism in Kidney Development and Polycystic Kidney Disease
… suggesting other genes/processes are involved. Lkb1 is a serine-threonine kinase involved in the regulation of several molecular processes including cellular polarity, autophagy, mTOR signaling, and energetic stress response, all of which are dysregulated in PKD. We generated mice lacking Lkb1 …
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The AMPK signalling pathway in cancer and DNA damage
… AMPK acts downstream of the tumour suppressor LKB1, that the AMPK signalling pathway is down-regulated in some tumours, and that diabetics treated with the AMPK-activating drug metformin exhibit a lower incidence of cancer. These results suggest that AMPK may itself be a tumour suppressor, …
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Role of protein kinase C isozymes in cellular senescence and reversal of senescence in response to 12-O-tetradecanoylphorbol-13 acetate (TPA) treatment in
… and NRF1 expressions through the activations of LKB1 and AMPK due to increased activity of PKCζ in old cells. These signaling pathways are important in regulating the mitochondrial encoding OXPHOS complex subunit genes and respiration as well as ATP generation, evidenced by employing siRNA …
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Nutritional status dictates the rate and mode of intestinal epithelial stem cell proliferation through an AMPK dependent mechanism
… known to be involved in obesity and growth, LKB1-AMPK, on the mode of division was tested. Consistent with our in vivo results, high glucose conditions greatly increased the % of symmetrically dividing cells compared with low glucose conditions. Inhibiting LKB1-AMPK blocks the normal switch …
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AMP-activated protein kinase kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of sedentary and endurance trained rats
… frequencies of 0.4/sec and 1/sec. Gastrocnemius LKB1 protein, a putative component of the AMPKK complex (LKB1, STRAD, and MO25), increased approximately 2-fold in response to training. Phosphorylation of AMPK determined by western blot was increased at both stimulation rates in both control and …
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Enhancing Radiation Sensitivity In Non-Small Cell Lung Cancer
… that trametinib selectively sensitized KRAS-LKB1 co-mutant NSCLC, but not KRAS-TP53 mutant cells, through radiation-induced senescence. In the LKB1 wild type background, trametinib and radiation activated AMPK-autophagy pathway to rescue cells from senescence, therefore conferring resistance …
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Mechanisms of Genome Buffering and Cell Fate Coordination in Adult Tissue Homeostasis
… to generate isogenic cells for the expression of LKB1, a tumor suppressor that regulates Wnt protein production, I encountered the emergence of foreign LKB1 proteins subsequent to the introduction of INDELs by the DNA editing enzyme CRISPR-Cas9. I demonstrate that these novel proteins are the …
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