Research Topics
Genomes and Genes
| Kun Liang GuanSummaryAffiliation: University of California Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Generation of acetyllysine antibodies and affinity enrichment of acetylated peptidesKun 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...
Amino acid signaling in TOR activationJoungmok 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....
Critical roles for the TSC-mTOR pathway in β-cell functionHiroyuki 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...
An emerging role for TOR signaling in mammalian tissue and stem cell physiologyRyan 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...
TEAD mediates YAP-dependent gene induction and growth controlBin 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...
Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signalingFa 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...
Regulation of mTORC1 by the Rab and Arf GTPasesLi 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...
IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylationXiaoduo 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...
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...
The Hippo-YAP pathway in organ size control and tumorigenesis: an updated versionBin 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....
Angiomotin is a novel Hippo pathway component that inhibits YAP oncoproteinBin 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...
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...
The Hippo-YAP pathway: new connections between regulation of organ size and cancerBin 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...
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....
Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligaseWenqing 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...
Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROSYaohui 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...
Regulation of TORC1 by Rag GTPases in nutrient responseEunjung 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...
Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated proteinBin 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...
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1Joungmok 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...
The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiationIan 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...
The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTORDan 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...
YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29Karen 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...
MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in miceDenghong 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...
Mst out and HCC inBin 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...
Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagyJoungmok 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...
Organ size control by Hippo and TOR pathwaysKaren 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....
Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic fluxQijun 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...
Amino acid signalling upstream of mTORJenna 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)...
Amino acid signaling to TOR activation: Vam6 functioning as a Gtr1 GEFLi 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...
Harness the power: new insights into the inhibition of YAP/YorkieBin 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...
Nutrient sensing, metabolism, and cell growth controlHai 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...
The Hippo pathway: regulators and regulationsFa 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...
IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectivesHui 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 Grants
- The TSC-mTOR pathway in cellular and organismal energy metabolismKun 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. ..
- Rheb small GTPase signaling in tuberous sclerosisKun 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. ..
- TSC2 tumor suppressor protein in cell energy responseKun 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. ..
- PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTIONKun 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 ..
- Regulation of Ras and Rheb modification by GCN2Kun 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. ..
- PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTIONKun 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 ..
- Regulation and function of the YAP transcription co-activator oncoproteinKun Liang Guan; Fiscal Year: 2010..This proposal will study the molecular mechanism of YAP in tumorigenesis by promoting cell proliferation and inhibiting cell death. ..
- The TSC-mTOR pathway in cellular and organismal energy metabolismKun 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. ..
- PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTIONKun 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. ..
- PROTEIN PHOSPHORYLATION AND GROWTH FACTOR FUNCTIONKun 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. ..
- SIGNAL TRANSDUCTION OF THE RAS FAMILY SMALL GTPASESKun 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 ..
- S6K and mTOR as targets for tuberous sclerosisKun 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. ..
