Kun Liang Guan

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc An emerging role for TOR signaling in mammalian tissue and stem cell physiology
    Ryan C Russell
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093 0815, USA
    Development 138:3343-56. 2011
  2. doi request reprint Amino acid signaling in TOR activation
    Joungmok Kim
    Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA
    Annu Rev Biochem 80:1001-32. 2011
  3. pmc Critical roles for the TSC-mTOR pathway in β-cell function
    Hiroyuki Mori
    Dept of Pharmacology and Moores Cancer Center, Univ of California San Diego, La Jolla, CA 92093 081, USA
    Am J Physiol Endocrinol Metab 297:E1013-22. 2009
  4. doi request reprint Generation of acetyllysine antibodies and affinity enrichment of acetylated peptides
    Kun Liang Guan
    State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan Unversity, Shanghai, China
    Nat Protoc 5:1583-95. 2010
  5. pmc Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling
    Fa Xing Yu
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
    Cell 150:780-91. 2012
  6. pmc TEAD mediates YAP-dependent gene induction and growth control
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 22:1962-71. 2008
  7. doi request reprint ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase
    Ryan C Russell
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA
    Nat Cell Biol 15:741-50. 2013
  8. pmc Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation
    Fa Xing Yu
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 27:1223-32. 2013
  9. pmc Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) is a negative regulator of the mammalian target of rapamycin complex 1 (mTORC1)
    Li Li
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 288:703-8. 2013
  10. pmc IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation
    Xiaoduo Xie
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:6474-9. 2011

Collaborators

Detail Information

Publications36

  1. pmc An emerging role for TOR signaling in mammalian tissue and stem cell physiology
    Ryan C Russell
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093 0815, USA
    Development 138:3343-56. 2011
    ..Here, we discuss the molecular mechanisms of TOR signaling and review recent in vitro and in vivo studies of mTOR tissue-specific activities in mammals...
  2. doi request reprint Amino acid signaling in TOR activation
    Joungmok Kim
    Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA
    Annu Rev Biochem 80:1001-32. 2011
    ....
  3. pmc Critical roles for the TSC-mTOR pathway in β-cell function
    Hiroyuki Mori
    Dept of Pharmacology and Moores Cancer Center, Univ of California San Diego, La Jolla, CA 92093 081, USA
    Am J Physiol Endocrinol Metab 297:E1013-22. 2009
    ..Thus, mTOR promulgates a dominant signal to promote β-cell/islet size and insulin production, and this pathway is crucial for β-cell function and glycemic control...
  4. doi request reprint Generation of acetyllysine antibodies and affinity enrichment of acetylated peptides
    Kun Liang Guan
    State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan Unversity, Shanghai, China
    Nat Protoc 5:1583-95. 2010
    ..The entire characterization procedure takes ∼2-3 d to complete...
  5. pmc Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling
    Fa Xing Yu
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
    Cell 150:780-91. 2012
    ..Our study identifies extracellular diffusible signals that modulate the Hippo pathway and also establishes the Hippo-YAP pathway as a critical signaling branch downstream of GPCR...
  6. pmc TEAD mediates YAP-dependent gene induction and growth control
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 22:1962-71. 2008
    ..Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP...
  7. doi request reprint ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase
    Ryan C Russell
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA
    Nat Cell Biol 15:741-50. 2013
    ..Our study reveals a molecular link from ULK1 to activation of the autophagy-specific VPS34 complex and autophagy induction...
  8. pmc Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation
    Fa Xing Yu
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 27:1223-32. 2013
    ..Taken together, our study demonstrates that Hippo-YAP is a key signaling branch of cAMP and PKA and reveals new insight into mechanisms of PKA in regulating a broad range of cellular functions...
  9. pmc Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) is a negative regulator of the mammalian target of rapamycin complex 1 (mTORC1)
    Li Li
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 288:703-8. 2013
    ..In addition, we found that MARK4 phosphorylates Raptor, a key component of mTORC1, and this phosphorylation may interfere with Raptor-Rag interaction. Our data demonstrate MARK4 as a new negative regulator of mTORC1...
  10. pmc IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation
    Xiaoduo Xie
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:6474-9. 2011
    ..Our observations suggest a physiological function of IKKε/TBK1 in AKT regulation and a possible mechanism of IKKε/TBK1 in oncogenesis by activating AKT...
  11. pmc Regulation of mTORC1 by the Rab and Arf GTPases
    Li Li
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 285:19705-9. 2010
    ..Our data demonstrate a key role of Rab and Arf family small GTPases and intracellular trafficking in mTORC1 activation, particularly in response to amino acids...
  12. pmc The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 24:862-74. 2010
    ....
  13. pmc Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein
    Bin Zhao
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 25:51-63. 2011
    ..These observations provide a potential link between the Hippo pathway and cell contact inhibition...
  14. pmc Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs)
    Jung Soon Mo
    Department of Pharmacology, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 26:2138-43. 2012
    ..PAR1 acts through G(12/13) and Rho GTPase to inhibit the Lats1/2 kinase. Our observations establish thrombin as a physiological signal for the Hippo pathway and implicate Hippo-YAP as a key downstream signaling branch of PAR activation...
  15. pmc The Hippo-YAP pathway: new connections between regulation of organ size and cancer
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093 0815, USA
    Curr Opin Cell Biol 20:638-46. 2008
    ..Dysregulation of the Hippo pathway contributes to the loss of contact inhibition observed in cancer cells. Therefore, the Hippo-YAP pathway connects the regulation of organ size and tumorigenesis...
  16. pmc A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP)
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093 0815, USA
    Genes Dev 24:72-85. 2010
    ....
  17. doi request reprint Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS
    Yaohui Chen
    State Key Laboratory of Genetic Engineering, School of Life Science, Novartis Fudan Joint Research Laboratory, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
    EMBO Rep 12:534-41. 2011
    ..These results reveal a new post-translational regulation of SOD2 by means of acetylation and SIRT3-dependent deacetylation in response to oxidative stress...
  18. doi request reprint Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase
    Wenqing Jiang
    State Key Laboratory of Genetic Engineering, School of Life Sciences, Medical College, Fudan University, Shanghai 20032, China
    Mol Cell 43:33-44. 2011
    ..Given that increased levels of PEPCK are linked with type II diabetes, this study also identifies potential therapeutic targets for diabetes...
  19. pmc Regulation of TORC1 by Rag GTPases in nutrient response
    Eunjung Kim
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093 081, USA
    Nat Cell Biol 10:935-45. 2008
    ..Genetic studies in Drosophila also show that Rag GTPases regulate cell growth, autophagy and animal viability during starvation. Our studies establish a function of Rag GTPases in TORC1 activation in response to amino acid signals...
  20. doi request reprint AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
    Joungmok Kim
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92130, USA
    Nat Cell Biol 13:132-41. 2011
    ..This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling...
  21. doi request reprint Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093 0815, USA
    Cancer Res 69:1089-98. 2009
    ..Our data suggest a model in which YAP induces gene expression and exerts its biological functions by interacting with transcription factors through both the TEAD-binding and WW domains...
  22. pmc The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation
    Ian Lian
    Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 24:1106-18. 2010
    ..Moreover, YAP binds directly to promoters of a large number of genes known to be important for stem cells and stimulates their expression. Our observations establish a critical role of YAP in maintaining stem cell pluripotency...
  23. doi request reprint Amino acid signalling upstream of mTOR
    Jenna L Jewell
    Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA
    Nat Rev Mol Cell Biol 14:133-9. 2013
    ..Recently, a model has emerged whereby mTORC1 activation occurs at the lysosome and is mediated through an amino acid sensing cascade involving RAG GTPases, Ragulator and vacuolar H(+)-ATPase (v-ATPase)...
  24. ncbi request reprint YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29
    Karen Tumaneng
    Department of Pharmacology and Moores Cancer Center, School of Medicine, University of California at San Diego, La Jolla, California 92093, USA
    Nat Cell Biol 14:1322-9. 2012
    ..Our studies reveal a functional link between Hippo and PI(3)K–mTOR, providing a molecular basis for the coordination of these two pathways in organ size regulation...
  25. pmc The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR
    Dan Egan
    Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, University of California at San Diego, La Jolla, USA
    Autophagy 7:643-4. 2011
    ..These studies have revealed a molecular mechanism of ULK1 regulation by nutrient signals via the actions of AMPK and mTORC1...
  26. pmc MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice
    Denghong Zhang
    Department of Medicine, University of California San Diego, La Jolla, California 92093 0613, USA
    J Clin Invest 120:2805-16. 2010
    ..Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF...
  27. doi request reprint Mst out and HCC in
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093 0815, USA
    Cancer Cell 16:363-4. 2009
    ..2009) reported that Mst1/2 ablation leads to hepatocellular carcinomas. Unexpectedly, Mst1/2 may activate another kinase besides Lats1 and Lats2 to phosphorylate YAP, and the role of Mst1/2 in YAP regulation is cell type dependent...
  28. pmc The Hippo pathway: regulators and regulations
    Fa Xing Yu
    Department of Pharmacology, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 27:355-71. 2013
    ..Here, we review regulatory mechanisms of the Hippo pathway and discuss potential implications involved in different physiological and pathological conditions...
  29. pmc Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy
    Joungmok Kim
    Department of Oral Biochemistry and Molecular Biology, Research Center for Tooth and Periodontal Tissue Regeneration, School of Dentistry, Kyung Hee University, Seoul 130 701, Korea
    Cell 152:290-303. 2013
    ..Our study reveals an intricate molecular regulation of Vps34 complexes by AMPK in nutrient stress response and autophagy...
  30. pmc Organ size control by Hippo and TOR pathways
    Karen Tumaneng
    Department of Pharmacology and Sanford Consortium for Regenerative Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Curr Biol 22:R368-79. 2012
    ....
  31. doi request reprint Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux
    Qijun Wang
    State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences and Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China
    Science 327:1004-7. 2010
    ..It represents a metabolic regulatory mechanism conserved from bacteria to mammals...
  32. pmc Nutrient sensing, metabolism, and cell growth control
    Hai Xin Yuan
    Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA
    Mol Cell 49:379-87. 2013
    ..The interplay among nutrients, metabolites, gene expression, and protein modification are involved in the coordination of cell growth with extracellular and intracellular conditions...
  33. doi request reprint Amino acid signaling to TOR activation: Vam6 functioning as a Gtr1 GEF
    Li Li
    Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, 92093, USA
    Mol Cell 35:543-5. 2009
    ..In this issue of Molecular Cell, Binda et al. identify Vam6/Vps39 as a guanine nucleotide exchange factor for Gtr1, a Rag family GTPase, to promote TORC1 activation in response to amino acids...
  34. doi request reprint Harness the power: new insights into the inhibition of YAP/Yorkie
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093 0815, USA
    Dev Cell 16:321-2. 2009
    ..Two papers in this issue on Developmental Cell, by Badouel et al. and Nishioka et al., address this question...
  35. pmc Nutrient signaling to mTOR and cell growth
    Jenna L Jewell
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Trends Biochem Sci 38:233-42. 2013
    ..Here we review the current knowledge of nutrient-dependent regulation of mTORC1...
  36. doi request reprint IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives
    Hui Yang
    Molecular and Cell Biology Lab, Institutes of Biomedical Sciences and School of Life Sciences, Fudan University, Shanghai, P R China
    Clin Cancer Res 18:5562-71. 2012
    ..Therapeutically, unique features of IDH1 and IDH2 mutations make them good biomarkers and potential drug targets...

Research Grants43

  1. The TSC-mTOR pathway in cellular and organismal energy metabolism
    Kun Liang Guan; Fiscal Year: 2011
    ..This proposal will investigate the function of TSC-mTOR in affecting leptin signaling and appetite control. The information generated from this project will provide new insights into to appetite regulation, obesity, and diabetes. ..
  2. Rheb small GTPase signaling in tuberous sclerosis
    Kun Liang Guan; Fiscal Year: 2007
    ..4. To demonstrate Rheb as a key cellular target of FTI (famesyl transferase inhibitor) in cell growth inhibition. 5. To identify and characterize Rheb interacting proteins. ..
  3. TSC2 tumor suppressor protein in cell energy response
    Kun Liang Guan; Fiscal Year: 2007
    ..3. To elucidate the physiological functions of TSC2 phosphorylation by AMPK and GSK3 in cellular energy response. 4. To investigate the mechanism of TSC2 in energy starvation-induced cell death. ..
  4. PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTION
    Kun Liang Guan; Fiscal Year: 2009
    ..To determine the functional significance of Sin1 phosphorylation in regulation of TORC2 2. To determine the regulation of Sin1 protein levels by Rictor and mTOR 3. To investigate the mechanisms of TORC2 activation by insulin and PI3K ..
  5. Regulation of Ras and Rheb modification by GCN2
    Kun Liang Guan; Fiscal Year: 2010
    ..The Ras family GTPases regulate normal cell growth but dysregulation can cause diseases, such as cancer. Our goal is to understand how Ras function is regulated. These studies may lead to new therapeutic treatment for cancer. ..
  6. PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTION
    Kun Liang Guan; Fiscal Year: 2010
    ..To determine the regulation of Sin1 protein levels by Rictor and mTOR 3. To investigate the mechanisms of TORC2 activation by insulin and PI3K ..
  7. Regulation and function of the YAP transcription co-activator oncoprotein
    Kun Liang Guan; Fiscal Year: 2010
    ..This proposal will study the molecular mechanism of YAP in tumorigenesis by promoting cell proliferation and inhibiting cell death. ..
  8. The TSC-mTOR pathway in cellular and organismal energy metabolism
    Kun Liang Guan; Fiscal Year: 2010
    ..This proposal will investigate the function of TSC-mTOR in affecting leptin signaling and appetite control. The information generated from this project will provide new insights into to appetite regulation, obesity, and diabetes. ..
  9. PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTION
    Kun Liang Guan; Fiscal Year: 2006
    ..Biochemical and cell biological approaches will be used to investigate the regulation of TSC2 by phosphorylation in response to growth factor stimulation, nutrient and ATP depletion, and cellular stress conditions. ..
  10. PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTION
    Kun Liang Guan; Fiscal Year: 2001
    ..Biochemical, and cell and molecular biological approaches will be used to achieve these goals. Completion of this proposal will further our understanding of the Ras/MAP kinase signal transduction. ..
  11. SIGNAL TRANSDUCTION OF THE RAS FAMILY SMALL GTPASES
    Kun Liang Guan; Fiscal Year: 2003
    ..The specific aims are to examine: 1) Interaction between smgGDS and Ras-GDP; 2) Regulation of smgGDS activity by Ras; and 3) Role of smgGDS in Ras-GDP signal transduction ..
  12. S6K and mTOR as targets for tuberous sclerosis
    Kun Liang Guan; Fiscal Year: 2003
    ..To validate S6K as a key downstream effector of TSC1/ TSC2. Biochemical, molecular and cell biological approaches will be used to accomplish these specific aims. ..