LKB1

Summary

Gene Symbol: LKB1
Description: serine/threonine kinase 11
Alias: LKB1, PJS, hLKB1, serine/threonine-protein kinase STK11, liver kinase B1, polarization-related protein LKB1, renal carcinoma antigen NY-REN-19, serine/threonine-protein kinase 11, serine/threonine-protein kinase LKB1
Species: human

Top Publications

  1. ncbi Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase
    D E Jenne
    Department of Neuroimmunology, Max Planck Institute of Psychiatry, Martinsried, Germany
    Nat Genet 18:38-43. 1998
  2. pmc Somatic LKB1 mutations promote cervical cancer progression
    Shana N Wingo
    Division of Gynecologic Oncology, UT Southwestern Medical Center, Dallas, TX, USA
    PLoS ONE 4:e5137. 2009
  3. ncbi Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung
    Montserrat Sanchez-Cespedes
    Department of Otolaryngology Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    Cancer Res 62:3659-62. 2002
  4. pmc The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School, and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:3329-35. 2004
  5. ncbi Analysis of the LKB1-STRAD-MO25 complex
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland
    J Cell Sci 117:6365-75. 2004
  6. pmc LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and prenylated in vivo
    S P Collins
    Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
    Biochem J 345:673-80. 2000
  7. pmc Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 370:849-57. 2003
  8. ncbi Stability of the Peutz-Jeghers syndrome kinase LKB1 requires its binding to the molecular chaperones Hsp90/Cdc37
    Pascale Nony
    Laboratoire Génétique et Cancer, FRE 2692, Domaine Rockefeller, 8, avenue Rockefeller, 69373 Lyon Cedex 08, France
    Oncogene 22:9165-75. 2003
  9. doi Possible involvement of LKB1-AMPK signaling in non-homologous end joining
    A Ui
    1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan 2 Division of Dynamic Proteome, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
    Oncogene 33:1640-8. 2014
  10. ncbi Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families
    A M Westerman
    Department of Internal Medicine II, University Hospital Rotterdam Dijkzigt, The Netherlands
    Hum Mutat 13:476-81. 1999

Research Grants

  1. THE ROLE OF PEUTZ JEGHER GENE IN APOPTOSIS
    Junying Yuan; Fiscal Year: 2005
  2. The role of LKB1 in the maintenance of genomic stability.
    Zhi Xiang Xu; Fiscal Year: 2013
  3. George Souroullas; Fiscal Year: 2014
  4. MOUSE MODEL FOR THE PEUTZ JEGHERS SYNDROME
    Marsha Frazier; Fiscal Year: 2002
  5. David J Kwiatkowski; Fiscal Year: 2016
  6. A kinase pathway required for cortical neuron polarization
    Franck Polleux; Fiscal Year: 2012
  7. Chemoprevention of Peutz-Jeghers Polyposis in a Mouse Model by Niclosamide
    Chongjuan Wei; Fiscal Year: 2012
  8. Shelley L Berger; Fiscal Year: 2016
  9. ADSS1 inactivation as a promoter of tumor metabolism and lung carcinogenesis
    Christopher R Herzog; Fiscal Year: 2010
  10. JOSE M TEIXEIRA; Fiscal Year: 2016

Detail Information

Publications215 found, 100 shown here

  1. ncbi Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase
    D E Jenne
    Department of Neuroimmunology, Max Planck Institute of Psychiatry, Martinsried, Germany
    Nat Genet 18:38-43. 1998
    ..We conclude that germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, cause the manifestations of PJ syndrome...
  2. pmc Somatic LKB1 mutations promote cervical cancer progression
    Shana N Wingo
    Division of Gynecologic Oncology, UT Southwestern Medical Center, Dallas, TX, USA
    PLoS ONE 4:e5137. 2009
    ..Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor...
  3. ncbi Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung
    Montserrat Sanchez-Cespedes
    Department of Otolaryngology Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    Cancer Res 62:3659-62. 2002
    ..Here we performed fine mapping of the short arm of chromosome 19 and found that the LKB1/STK11 gene mapped in the minimal-deleted region...
  4. pmc The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School, and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:3329-35. 2004
    ..Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant ..
  5. ncbi Analysis of the LKB1-STRAD-MO25 complex
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland
    J Cell Sci 117:6365-75. 2004
    Mutations in the LKB1 tumour suppressor threonine kinase cause the inherited Peutz-Jeghers cancer syndrome and are also observed in some sporadic cancers...
  6. pmc LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and prenylated in vivo
    S P Collins
    Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
    Biochem J 345:673-80. 2000
    ..The human LKB1 (hLKB1) gene encodes a serine/threonine protein kinase that is deficient in the majority of patients with PJS...
  7. pmc Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 370:849-57. 2003
    b>LKB1 is a widely expressed serine/threonine protein kinase that is mutated in the inherited Peutz-Jeghers cancer syndrome...
  8. ncbi Stability of the Peutz-Jeghers syndrome kinase LKB1 requires its binding to the molecular chaperones Hsp90/Cdc37
    Pascale Nony
    Laboratoire Génétique et Cancer, FRE 2692, Domaine Rockefeller, 8, avenue Rockefeller, 69373 Lyon Cedex 08, France
    Oncogene 22:9165-75. 2003
    ..Inactivating germline mutations of the LKB1 gene, which encodes a serine/threonine kinase, are responsible for the majority of PJS cases...
  9. doi Possible involvement of LKB1-AMPK signaling in non-homologous end joining
    A Ui
    1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan 2 Division of Dynamic Proteome, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
    Oncogene 33:1640-8. 2014
    b>LKB1/STK11 is a tumor suppressor gene responsible for Peutz-Jeghers syndrome, an inherited cancer disorder associated with genome instability...
  10. ncbi Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families
    A M Westerman
    Department of Internal Medicine II, University Hospital Rotterdam Dijkzigt, The Netherlands
    Hum Mutat 13:476-81. 1999
    ..The recently identified LKB1/STK11 gene located at chromosome 19p13.3 is mutated in a number of PJS pedigrees...
  11. ncbi LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes
    Hamid Mehenni
    Departement de Biologie Cellulaire, Universite de Geneve, 1211 Geneve 4, Switzerland
    Hum Mol Genet 14:2209-19. 2005
    Germline mutations of the LKB1 (STK11) tumor suppressor gene lead to Peutz-Jeghers syndrome (PJS) and predisposition to cancer. LKB1 encodes a serine/threonine kinase generally inactivated in PJS patients...
  12. ncbi Enhanced expression of LKB1 in breast cancer cells attenuates angiogenesis, invasion, and metastatic potential
    Zhi gang Zhuang
    Breast Cancer Institute, Cancer Hospital, Department of Oncology, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, Shanghai, People s Republic of China
    Mol Cancer Res 4:843-9. 2006
    b>LKB1 (also known as STK11) is a recently identified tumor suppressor gene whose mutation can lead to Peutz-Jeghers syndrome, which is characterized by gastrointestinal polyps and cancers of different organ systems...
  13. ncbi LKB1 catalytically deficient mutants enhance cyclin D1 expression
    Kristine D Scott
    Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
    Cancer Res 67:5622-7. 2007
    Mutations in the serine-threonine tumor-suppressor kinase LKB1 are responsible for Peutz-Jeghers syndrome, characterized by hamartomatous proliferation and an increased risk of developing cancer...
  14. pmc Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis
    Derrick J Rossi
    Haartman Institute and Helsinki University Central Hospital, Biomedicum Helsinki, P O Box 63, University of Helsinki, 00014 Helsinki, Finland
    Proc Natl Acad Sci U S A 99:12327-32. 2002
    Inactivating germ-line mutations of LKB1 lead to Peutz-Jeghers syndrome (PJS). We have generated mice heterozygous for a targeted inactivating allele of Lkb1 and found that they develop severe gastrointestinal polyposis...
  15. ncbi Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer
    G R Bignell
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Cancer Res 58:1384-6. 1998
    Germ-line mutations in the LKB1 gene on chromosome 19p are responsible for most cases of the Peutz-Jeghers syndrome, in which intestinal hamartomas are associated with elevated risks of several cancer types, including breast cancer...
  16. ncbi Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma
    P Guldberg
    Department of Tumour Cell Biology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen
    Oncogene 18:1777-80. 1999
    Mutations in LKB1/STK11, a gene mapping to chromosome 19p13.3 and encoding a widely expressed serine/threonine kinase, were recently identified as the cause of Peutz-Jeghers syndrome...
  17. ncbi Mutation screening at the RNA level of the STK11/LKB1 gene in Peutz-Jeghers syndrome reveals complex splicing abnormalities and a novel mRNA isoform (STK11 c.597(insertion mark)598insIVS4)
    A A Abed
    Department of Internal Medicine MGO Biocenter, University Halle Wittenberg, Halle, Germany
    Hum Mutat 18:397-410. 2001
    ..test for the identification of germline mutations in the serine/threonine protein kinase 11 (STK11, also designated LKB1) gene in Peutz-Jeghers syndrome (PJS)...
  18. ncbi The molecular mechanisms that underlie the tumor suppressor function of LKB1
    Dahua Fan
    Department of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, China
    Acta Biochim Biophys Sin (Shanghai) 41:97-107. 2009
    Germline mutations of the LKB1 tumor suppressor gene result in Peutz-Jeghers syndrome (PJS) characterized by intestinal hamartomas and increased incidence of epithelial cancers...
  19. pmc LKB1 suppresses p21-activated kinase-1 (PAK1) by phosphorylation of Thr109 in the p21-binding domain
    Atsuko Deguchi
    Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    J Biol Chem 285:18283-90. 2010
    The serine/threonine protein kinase LKB1 is a tumor suppressor gene mutated in Peutz-Jeghers syndrome patients. The mutations are found also in several types of sporadic cancer...
  20. ncbi Wnt signaling may be activated in a subset of Peutz-Jeghers syndrome polyps closely correlating to LKB1 expression
    Yamei Ma
    Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China
    Oncol Rep 23:1569-76. 2010
    ..The major gene responsible for PJS is LKB1. LKB1 has a complex cellular role, therefore, the exact role of LKB1 in Peutz-Jeghers syndrome hamartomas (PJSs) is ..
  21. pmc Loss of the tumor suppressor LKB1 promotes metabolic reprogramming of cancer cells via HIF-1α
    Brandon Faubert
    Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada H3A 1A3
    Proc Natl Acad Sci U S A 111:2554-9. 2014
    ..The liver kinase B1 (LKB1) is a serine/threonine kinase and tumor suppressor that couples bioenergetics to cell-growth control ..
  22. doi Evaluation of the contribution of the three breast cancer susceptibility genes CHEK2, STK11, and PALB2 in non-BRCA1/2 French Canadian families with high risk of breast cancer
    Frederic Guenard
    Cancer Genomics Laboratory, Department of Molecular Medicine, Laval University, Quebec City, Quebec, Canada
    Genet Test Mol Biomarkers 14:515-26. 2010
    ....
  23. pmc Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated phosphorylation of LKB1/STK11 at Thr-366
    Gopal P Sapkota
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem J 368:507-16. 2002
    The serine/threonine protein kinase LKB1 functions as a tumour suppressor, and mutations in this enzyme lead to the inherited Peutz-Jeghers cancer syndrome...
  24. doi LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis
    Pekka Katajisto
    Genome Scale Biology Program and Institute of Biomedicine, Biomedicum Helsinki, 00014 University of Helsinki, Finland
    Nat Genet 40:455-9. 2008
    Germline mutations in STK11 (also known as LKB1) are found in individuals with Peutz-Jeghers syndrome (PJS) manifesting with gastrointestinal polyps that contain a prominent stromal component...
  25. pmc Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity
    H Mehenni
    Division of Medical Genetics, University of Geneva Medical School, Geneva, Switzerland
    Am J Hum Genet 63:1641-50. 1998
    ..The PJS gene on 19p13.3 has recently been cloned, and it encodes the serine/threonine kinase LKB1. The gene, which is ubiquitously expressed, is composed of 10 exons spanning 23 kb...
  26. pmc MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1
    Thomas Timm
    Max Planck Unit for Structural Molecular Biology, Notkestrasse 85, D 22607 Hamburg, Germany
    EMBO J 22:5090-101. 2003
    ..Overexpression of MARK eventually leads to microtubule breakdown and cell death, but in neuronal cells the primary effect is to allow the development of neurites during differentiation...
  27. ncbi High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome
    Stefan Aretz
    Institute of Human Genetics, University of Bonn, Bonn, Germany
    Hum Mutat 26:513-9. 2005
    Germline mutations in the STK11 gene have been identified in 10-70% of patients with Peutz-Jeghers syndrome (PJS), an autosomal-dominant hamartomatous polyposis syndrome. A second locus was assumed in a large proportion of PJS patients...
  28. pmc MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 22:5102-14. 2003
    Mutations in the LKB1 protein kinase result in the inherited Peutz Jeghers cancer syndrome. LKB1 has been implicated in regulating cell proliferation and polarity although little is known about how this enzyme is regulated...
  29. pmc STRADalpha regulates LKB1 localization by blocking access to importin-alpha, and by association with Crm1 and exportin-7
    Julia Dorfman
    Program in Biophysics, Department of Microbiology, University of Virginia School of Medicine, Charlottesville VA 22908 0577, USA
    Mol Biol Cell 19:1614-26. 2008
    b>LKB1, a serine/threonine kinase, regulates cell polarity, metabolism, and cell growth. The activity and cellular distribution of LKB1 are determined by cofactors, STRADalpha and MO25...
  30. ncbi LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest
    P A Marignani
    Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 276:32415-8. 2001
    Inactivating mutations in the serine-threonine kinase LKB1 (STK11) are found in most patients with Peutz-Jeghers syndrome; however the function of LKB1 is unknown...
  31. ncbi A serine/threonine kinase gene defective in Peutz-Jeghers syndrome
    A Hemminki
    Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland
    Nature 391:184-7. 1998
    ..This previously identified but unmapped gene, LKB1, has strong homology to a cytoplasmic Xenopus serine/threonine protein kinase XEEK1, and weaker similarity to many ..
  32. ncbi LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1
    D P Smith
    The Breakthrough Toby Robins Breast Cancer Research Centre, London, UK
    Hum Mol Genet 10:2869-77. 2001
    b>LKB1 is a serine/threonine kinase which is inactivated by mutation in the Peutz-Jeghers polyposis and cancer predisposition syndrome (PJS). We have identified a novel leucine-rich repeat containing protein, LIP1, that interacts with LKB1...
  33. pmc Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD
    A F Baas
    Hubrecht Laboratory, Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    EMBO J 22:3062-72. 2003
    The LKB1 gene encodes a serine/threonine kinase mutated in Peutz-Jeghers cancer syndrome. Despite several proposed models for LKB1 function in development and in tumour suppression, the detailed molecular action of LKB1 remains undefined...
  34. ncbi Relative frequency and morphology of cancers in STK11 mutation carriers
    Wendy Lim
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
    Gastroenterology 126:1788-94. 2004
    There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS).
  35. doi LKB1; linking cell structure and tumor suppression
    A F Hezel
    Department of Medicine, Harvard Medical School, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    Oncogene 27:6908-19. 2008
    Germ line mutations in the LKB1 tumor suppressor gene are associated with the Peutz-Jeghers polyposis and cancer syndrome. Somatic mutations in Lkb1 are observed in sporadic pulmonary, pancreatic and biliary cancers and melanomas...
  36. ncbi IGF-1 phosphorylates AMPK-alpha subunit in ATM-dependent and LKB1-independent manner
    Atsushi Suzuki
    Cancer Physiology Project, National Cancer Center Research Institute East, 6 5 1 Kashiwanoha, Kashiwa, Chiba 277 8577, Japan
    Biochem Biophys Res Commun 324:986-92. 2004
    ..Recently, the tumor suppressor serine/threonine protein kinase LKB1 was identified as an upstream kinases, AMPKKs...
  37. ncbi Distinctive gene expression of human lung adenocarcinomas carrying LKB1 mutations
    Paloma Fernandez
    Lymphomas and Lung Cancer Laboratory, Spanish National Cancer Centre CNIO, Madrid, Spain
    Oncogene 23:5084-91. 2004
    b>LKB1, a tumor-suppressor gene that codifies for a serine/threonine kinase, is mutated in the germ-line of patients affected with the Peutz-Jeghers syndrome (PJS), which have an increased incidence of several cancers including ..
  38. pmc Genotype-phenotype correlations in Peutz-Jeghers syndrome
    C I Amos
    Department of Epidemiology, U T M D Anderson Cancer Center HMB, Houston 77030, USA
    J Med Genet 41:327-33. 2004
    Peutz-Jeghers syndrome (PJS) is a dominantly inherited disorder often caused by mutations in STK11...
  39. ncbi A novel STK11 germline mutation in two siblings with Peutz-Jeghers syndrome complicated by primary gastric cancer
    K Shinmura
    First Department of Pathology, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Shizuoka, Japan
    Clin Genet 67:81-6. 2005
    Patients with Peutz-Jeghers syndrome (PJS) are known to be at risk of gastric cancer (GC), and the STK11 gene is a susceptibility gene for PJS...
  40. pmc Sequence changes in predicted promoter elements of STK11/LKB1 are unlikely to contribute to Peutz-Jeghers syndrome
    Nicholas C M Hearle
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK
    BMC Genomics 6:38. 2005
    Germline mutations or large-scale deletions in the coding region and splice sites of STK11/LKB1 do not account for all cases of Peutz-Jeghers syndrome (PJS)...
  41. pmc Exonic STK11 deletions are not a rare cause of Peutz-Jeghers syndrome
    N C M Hearle
    J Med Genet 43:e15. 2006
    Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant cancer predisposition syndrome characterised by oro-facial pigmentation and hamartomatous polyposis of the gastrointestinal tract...
  42. ncbi LKB1/STK11 suppresses cyclooxygenase-2 induction and cellular invasion through PEA3 in lung cancer
    Sunil Upadhyay
    Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
    Cancer Res 66:7870-9. 2006
    We showed that the PEA3 transcriptional factor interacted with LKB1, a serine/threonine kinase, which is somatically mutated in lung cancer. This interaction occurred through the ETS domain of PEA3 and the kinase domain of LKB1...
  43. ncbi A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome
    M Sanchez-Cespedes
    Molecular Pathology Programme, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro, Madrid, Spain
    Oncogene 26:7825-32. 2007
    Germline LKB1 mutations are responsible for Peutz-Jeghers syndrome (PJS)...
  44. doi Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex
    Jean Paul ten Klooster
    Hubrecht Institute, KNAW and University Medical Centre, Utrecht, The Netherlands
    Dev Cell 16:551-62. 2009
    The human Lkb1 kinase, encoded by the ortholog of the invertebrate Par4 polarity gene, is mutated in Peutz-Jeghers cancer syndrome. Lkb1 activity requires complex formation with the pseudokinase Strad and the adaptor protein Mo25...
  45. ncbi Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis
    A Hemminki
    Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland
    Nat Genet 15:87-90. 1997
    ..The study demonstrates the power of CGH combined with LOH analysis in identifying putative tumour suppressor loci, and provides molecular evidence of malignant potential in hamartomas...
  46. ncbi Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome
    H Nakagawa
    Department of Clinical Genetics, Biomedical Research Center, Osaka University, Japan
    Hum Genet 103:168-72. 1998
    Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary disease characterized by hamartomatous polyposis involving the entire bowel. Recently STK11, a gene bearing a mutation responsible for PJS, was isolated...
  47. pmc Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers
    G H Su
    Departments of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Am J Pathol 154:1835-40. 1999
    ..It was recently shown that germline mutations of the STK11/LKB1 gene are responsible for PJS...
  48. pmc The regulation of AMP-activated protein kinase by phosphorylation
    S C Stein
    Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, U K
    Biochem J 345:437-43. 2000
    ..Furthermore, we provide evidence that phosphorylation of Thr(172) may be involved in the sensitivity of the AMPK complex to AMP...
  49. pmc STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas
    N Sato
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
    Am J Pathol 159:2017-22. 2001
    ..Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of ..
  50. ncbi Functional analysis of LKB1/STK11 mutants and two aberrant isoforms found in Peutz-Jeghers Syndrome patients
    J Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    Hum Mutat 21:172. 2003
    ..PJS) is thought to be caused by mutations occurring in the widely expressed serine/threonine protein kinase named LKB1/STK11...
  51. ncbi Regulation of the Wnt signalling component PAR1A by the Peutz-Jeghers syndrome kinase LKB1
    James Spicer
    Cancer Research UK Gene Function and Regulation Group, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK
    Oncogene 22:4752-6. 2003
    Loss-of-function mutations in the LKB1 (STK11) serine-threonine kinase gene cause Peutz-Jeghers syndrome, which is associated with inherited susceptibility to colorectal and other cancers...
  52. ncbi LKB1 protein expression in the evolution of glandular neoplasia of the lung
    Hassan Ghaffar
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Clin Cancer Res 9:2998-3003. 2003
    About one-third of sporadic lung adenocarcinomas demonstrates biallelic inactivation of the LKB1 gene, but the timing of this event is not known.
  53. pmc Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    Simon A Hawley
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, UK
    J Biol 2:28. 2003
    ..Although they do not have obvious mammalian homologs, they are related to LKB1, a tumor suppressor that is mutated in the human Peutz-Jeghers cancer syndrome...
  54. pmc Restoration of silenced Peutz-Jeghers syndrome gene, LKB1, induces apoptosis in pancreatic carcinoma cells
    Suparna Qanungo
    Department of Research, MetroHealth Medical Center, Cleveland, OH 44109, USA
    Neoplasia 5:367-74. 2003
    Germ line mutations of the LKB1 tumor suppressor gene lead to Peutz-Jeghers syndrome (PJS) with a predisposition to cancer...
  55. pmc LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 23:833-43. 2004
    We recently demonstrated that the LKB1 tumour suppressor kinase, in complex with the pseudokinase STRAD and the scaffolding protein MO25, phosphorylates and activates AMP-activated protein kinase (AMPK)...
  56. ncbi An LKB1 AT-AC intron mutation causes Peutz-Jeghers syndrome via splicing at noncanonical cryptic splice sites
    Michelle L Hastings
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Struct Mol Biol 12:54-9. 2005
    ..PJS is caused by germline mutations in the tumor suppressor gene LKB1. One such mutation, IVS2+1A>G, alters the second intron 5' splice site, which has sequence features of a U12-..
  57. ncbi Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate
    Mahaboobi Jaleel
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    FEBS Lett 579:1417-23. 2005
    Recent work has shown that the LKB1 tumour suppressor protein kinase phosphorylates and activates protein kinases belonging to the AMP activated kinase (AMPK) subfamily...
  58. ncbi Functional analysis of Peutz-Jeghers mutations reveals that the LKB1 C-terminal region exerts a crucial role in regulating both the AMPK pathway and the cell polarity
    Christelle Forcet
    Laboratoire Génétique Moléculaire, Signalisation et Cancer, CNRS UMR 5201, Domaine Rockfeller, Lyon, France
    Hum Mol Genet 14:1283-92. 2005
    Germline mutations of the LKB1 gene are responsible for the cancer-prone Peutz-Jeghers syndrome (PJS). LKB1 encodes a serine-threonine kinase that acts as a regulator of cell cycle, metabolism and cell polarity...
  59. ncbi Reactive lipid species from cyclooxygenase-2 inactivate tumor suppressor LKB1/STK11: cyclopentenone prostaglandins and 4-hydroxy-2-nonenal covalently modify and inhibit the AMP-kinase kinase that modulates cellular energy homeostasis and protein translati
    Tracy M Wagner
    Department of Medicinal Chemistry, University of Utah, Huntsman Cancer Institute, Salt Lake City, Utah 84112, USA
    J Biol Chem 281:2598-604. 2006
    b>LKB1, a unique serine/threonine kinase tumor suppressor, modulates anabolic and catabolic homeostasis, cell proliferation, and organ polarity. Chemically reactive lipids, e.g...
  60. ncbi Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells
    Zhonglin Xie
    Division of Endocrinology and Diabetes, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA
    J Biol Chem 281:6366-75. 2006
    ..In contrast, ONOO- activated PKCzeta in LKB1-deficient HeLa-S3 but affected neither AMPK-Thr172 nor AMPK activity...
  61. pmc A novel mutation of STK11/LKB1 gene leads to the loss of cell growth inhibition in head and neck squamous cell carcinoma
    W Qiu
    Department of Otolaryngology and Head and Neck Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Oncogene 25:2937-42. 2006
    To investigate whether genetic alteration of the STK11 (serine/threonine kinase 11)/LKB1 tumor-suppressor gene is involved in the carcinogenesis of head and neck squamous cell carcinoma (HNSCC), the entire encoding exons and flanking ..
  62. ncbi The tumor suppressor LKB1 induces p21 expression in collaboration with LMO4, GATA-6, and Ldb1
    Takeshi Setogawa
    Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 0032, Japan
    Biochem Biophys Res Commun 343:1186-90. 2006
    The LKB1/STK11 serine/threonine kinase is mutated in Peutz-Jeghers syndrome and various sporadic cancers such as lung adenocarcinoma...
  63. pmc LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome
    E Volikos
    J Med Genet 43:e18. 2006
    b>LKB1/STK11 germline mutations cause Peutz-Jeghers syndrome (PJS)...
  64. ncbi Dysfunctional AMPK activity, signalling through mTOR and survival in response to energetic stress in LKB1-deficient lung cancer
    J Carretero
    Lung Cancer Group, Spanish National Cancer Centre CNIO, Madrid, Spain
    Oncogene 26:1616-25. 2007
    b>LKB1, mutated in Peutz-Jeghers and in sporadic lung tumours, phosphorylates a group of protein kinases named AMP-activated protein kinase (AMPK)-related kinases. Among them is included the AMPK, a sensor of cellular energy status...
  65. ncbi Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy
    Anna A Noga
    Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine and Dentistry, Univ of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Heart Circ Physiol 292:H1460-9. 2007
    AMP-activated protein kinase (AMPK) is a major metabolic regulator in the cardiac myocyte. Recently, LKB1 was identified as a kinase that regulates AMPK...
  66. ncbi LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activation
    Ping Yao Zeng
    Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania and Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P R China
    Cancer Res 66:10701-8. 2006
    The tumor suppressor LKB1 is an evolutionarily conserved serine/threonine kinase...
  67. pmc Interference with energy metabolism by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside induces HPV suppression in cervical carcinoma cells and apoptosis in the absence of LKB1
    Julia Nafz
    Angewandte Tumorvirologie, Abteilung Virale Transformationsmechanismen, Deutsches Krebsforschungszentrum, Heidelberg 69120, Germany
    Biochem J 403:501-10. 2007
    ..Moreover, the outcome of AICAR on proliferation and survival was dependent on p53 activation and the presence of LKB1, the major upstream kinase of AMPK...
  68. ncbi Suppression of tubulin polymerization by the LKB1-microtubule-associated protein/microtubule affinity-regulating kinase signaling
    Yasushi Kojima
    Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    J Biol Chem 282:23532-40. 2007
    b>LKB1, a tumor suppressor gene mutated in the Peutz-Jeghers syndrome, encodes a serine/threonine protein kinase...
  69. ncbi LKB1 modulates lung cancer differentiation and metastasis
    Hongbin Ji
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 448:807-10. 2007
    Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers...
  70. doi LKB1 protein expression in neuroendocrine tumors of the lung
    Randa Mahmoud Sobhi Amin
    Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Japan
    Pathol Int 58:84-8. 2008
    During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found...
  71. doi The tumor suppressor LKB1 regulates lung cancer cell polarity by mediating cdc42 recruitment and activity
    Shumin Zhang
    Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia 30043, USA
    Cancer Res 68:740-8. 2008
    The tumor suppressor LKB1 is mutated in 30% of non-small cell lung cancer (NSCLC) tumors and cell lines and is proposed to be a key regulator of epithelial cell polarity; however, how LKB1 regulates cancer cell polarity is not known...
  72. doi LKB1 and lung cancer: more than the usual suspects
    Usman Shah
    Departments of Medicine and Genetics, The Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
    Cancer Res 68:3562-5. 2008
    ..For LKB1, a more recently identified human tumor suppressor gene, however, the problem is different...
  73. pmc Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients
    J P Koivunen
    Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Br J Cancer 99:245-52. 2008
    Somatic mutations of LKB1 tumour suppressor gene have been detected in human cancers including non-small cell lung cancer (NSCLC)...
  74. pmc LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins
    Diansheng Zhong
    The Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Cancer Res 68:7270-7. 2008
    b>LKB1 plays the role of tumor suppressor, opposite to Akt, by negatively regulating mammalian target of rapamycin through the activation of AMP-activated protein kinase and TSC signaling...
  75. pmc LKB1 catalytic activity contributes to estrogen receptor alpha signaling
    Suchita Nath-Sain
    Faculty of Medicine, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada
    Mol Biol Cell 20:2785-95. 2009
    The tumor suppressor serine-threonine kinase LKB1 is mutated in Peutz-Jeghers syndrome (PJS) and in epithelial cancers, including hormone-sensitive organs such as breast, ovaries, testes, and prostate...
  76. pmc ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor
    Elton Zeqiraj
    Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, Scotland
    PLoS Biol 7:e1000126. 2009
    ..The pseudokinase STRAD activates the LKB1 tumour suppressor by forming a heterotrimeric complex with LKB1 and the scaffolding protein MO25...
  77. doi LKB1 and AMPK family signaling: the intimate link between cell polarity and energy metabolism
    Marnix Jansen
    Hubrecht Institute, Developmental Biology and Stem Cell Research, 3584 CT Utrecht, The Netherlands
    Physiol Rev 89:777-98. 2009
    Research on the LKB1 tumor suppressor protein mutated in cancer-prone Peutz-Jeghers patients has continued at a feverish pace following exciting developments linking energy metabolism and cancer development...
  78. pmc Mutations in STK11 gene in Czech Peutz-Jeghers patients
    Peter Vasovcak
    Department of Biology and Medical Genetics, Charles University 2nd Medical School, University Hospital Motol, Prague, Czech Republic
    BMC Med Genet 10:69. 2009
    Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis...
  79. pmc SIK1 couples LKB1 to p53-dependent anoikis and suppresses metastasis
    Hailing Cheng
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Sci Signal 2:ra35. 2009
    ..The presence of functional SIK1 was required for the activity of the kinase LKB1 in promoting p53-dependent anoikis and suppressing anchorage-independent growth, Matrigel invasion, and metastatic ..
  80. pmc Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation
    Elton Zeqiraj
    Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    Science 326:1707-11. 2009
    The LKB1 tumor suppressor is a protein kinase that controls the activity of adenosine monophosphate-activated protein kinase (AMPK)...
  81. ncbi Endogenous LKB1 knockdown accelerates G(1)/S transition through p53 and p16 pathways
    Xiaoyan Liang
    Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
    Cancer Biol Ther 9:156-60. 2010
    The tumor suppressor LKB1 is inactivated in 90% of Peutz-Jeghers cancer syndrome, 30-40% of non-small cell lung carcinoma, and a variety of other cancers, indicating the loss of LKB1 activity is a critical step in oncogenesis...
  82. doi Breakpoint determination of 15 large deletions in Peutz-Jeghers subjects
    Nicoletta Resta
    Dipartimento di Biomedicina dell Eta Evolutiva, Sezione di Genetica Medica, Università di Bari Aldo Moro, Policlinico Piazza G Cesare 11, 70124, Bari, Italy
    Hum Genet 128:373-82. 2010
    ..STK11/LKB1 (hereafter named STK11) germline mutations account for the large majority of PJS cases whereas large deletions ..
  83. pmc The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss
    Yan Feng
    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Cancer Res 72:6502-11. 2012
    Somatic mutation of the tumor suppressor gene LKB1 occurs frequently in lung cancer where it causes tumor progression and metastasis, but the underlying mechanisms remain mainly unknown...
  84. doi A computational multiscale model of glioblastoma growth: regulation of cell migration and proliferation via microRNA-451, LKB1 and AMPK
    Tina A Schuetz
    Institute of Medical Engineering, University of Luebeck, 23562 Luebeck, Germany
    Conf Proc IEEE Eng Med Biol Soc 2012:6620-3. 2012
    ..The network is based on recently published work on the interaction of microRNA-451, LKB1 and AMPK in the regulation of glioblastoma cell migration and proliferation...
  85. ncbi Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth
    G P Sapkota
    Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    J Biol Chem 276:19469-82. 2001
    ..The causative gene is a protein kinase termed LKB1, predicted to function as a tumor suppressor. The mechanism by which LKB1 is regulated in cells is not known...
  86. pmc Identification and characterization of four novel phosphorylation sites (Ser31, Ser325, Thr336 and Thr366) on LKB1/STK11, the protein kinase mutated in Peutz-Jeghers cancer syndrome
    Gopal P Sapkota
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 362:481-90. 2002
    ..The causative gene encodes a nuclear-localized protein kinase, termed LKB1, which is predicted to function as a tumour suppressor...
  87. pmc Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases
    Seung Pyo Hong
    Department of Genetics and Development, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 100:8839-43. 2003
    ..We further show that the closely related mammalian LKB1 kinase, which is associated with Peutz-Jeghers cancer-susceptibility syndrome, phosphorylates and activates AMPK in ..
  88. pmc Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome
    Michael N Corradetti
    Life Sciences Institute, Department of Biological Chemistry, and Institute of Gerontology, University of Michigan, Ann Arbor, Michigan 48109, USA
    Genes Dev 18:1533-8. 2004
    ..Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC...
  89. pmc The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation
    Mahaboobi Jaleel
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 394:545-55. 2006
    Recent work indicates that the LKB1 tumour suppressor protein kinase, which is mutated in Peutz-Jeghers cancer syndrome, phosphorylates and activates a group of protein kinases that are related to AMPK (AMP-activated protein kinase)...
  90. ncbi Activation of PAR-1 kinase and stimulation of tau phosphorylation by diverse signals require the tumor suppressor protein LKB1
    Ji Wu Wang
    Department of Pathology, Stanford University School of Medicine, and Geriatric Research, Education, and Clinical Center Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA
    J Neurosci 27:574-81. 2007
    ..Here we show that phosphorylation of PAR-1 by the tumor suppressor protein LKB1 is required for PAR-1 activation, which in turn promotes tau phosphorylation in Drosophila...
  91. pmc Prevalence and specificity of LKB1 genetic alterations in lung cancers
    S Matsumoto
    Biology Division, National Cancer Center Research Institute, 1 1 Tsukiji 5 chome, Chuo Ku, Tokyo 104 0045, Japan
    Oncogene 26:5911-8. 2007
    Germline LKB1 mutations cause Peutz-Jeghers syndrome, a hereditary disorder that predisposes to gastrointestinal hamartomatous polyposis and several types of malignant tumors...
  92. pmc Ovulatory response to treatment of polycystic ovary syndrome is associated with a polymorphism in the STK11 gene
    Richard S Legro
    Department of Obstetrics and Gynecology, Pennsylvania State University, M S Hershey Medical Center, 500 University Drive, H103, Hershey, Pennsylvania 17033, USA
    J Clin Endocrinol Metab 93:792-800. 2008
    ..Clomiphene and insulin sensitizers such as metformin are used to induce ovulation in polycystic ovary syndrome (PCOS), but the ovulatory response is variable, and the causes of this variation are poorly understood...
  93. doi Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer
    T Komiya
    Genetics Branch, National Cancer Institute and National Naval Medical Center, Bethesda, MD, USA
    Oncogene 29:1672-80. 2010
    ..As LKB1 is a target for mutational inactivation in lung cancer and was recently shown to regulate hepatic Crtc2/CREB ..
  94. pmc Homozygous deletion of the STK11/LKB1 locus and the generation of novel fusion transcripts in cervical cancer cells
    Michael T McCabe
    Department of Radiation Oncology, Emory University School of Medicine, 1365C Clifton Road, Atlanta, GA 30322 The Winship Cancer Institute of Emory University, 1365C Clifton Road, Atlanta, GA 30322
    Cancer Genet Cytogenet 197:130-41. 2010
    The STK11/LKB1 gene encodes a ubiquitously expressed serine/threonine kinase that is mutated in multiple sporadic cancers including non-small cell lung carcinomas, pancreatic cancers, and melanomas...
  95. pmc MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells
    Jakub Godlewski
    Dardinger Laboratory for Neuro oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University Medical Center and James Comprehensive Cancer Center, Columbus, OH 43210, USA
    Mol Cell 37:620-32. 2010
    ..The effects of miR-451 are mediated by LKB1, which it represses through targeting its binding partner, CAB39 (MO25 alpha)...
  96. pmc LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest
    Jennifer P Morton
    Beatson Institute for Cancer Research, Garscube Estate, Glasgow, UK
    Gastroenterology 139:586-97, 597.e1-6. 2010
    Patients carrying germline mutations of LKB1 have an increased risk of pancreatic cancer; however, it is unclear whether down-regulation of LKB1 is an important event in sporadic pancreatic cancer...
  97. doi The role of LKB1 and AMPK in cellular responses to stress and damage
    Angela Alexander
    Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Smithville, TX 78957, United States
    FEBS Lett 585:952-7. 2011
    The LKB1 and AMPK proteins participate in an energy sensing cascade that responds to depletion of ATP, serving as a master regulator of metabolism that inhibits anabolic processes and stimulates catabolic processes...
  98. pmc Frequent homozygous deletion of the LKB1/STK11 gene in non-small cell lung cancer
    R K Gill
    Laboratory of Human Carcinogenesis, Bethesda, MD, USA
    Oncogene 30:3784-91. 2011
    b>LKB1/STK11 is a tumor suppressor and a negative regulator of mammalian target of rapamycin signaling. It is inactivated in 30% of lung cancer cell lines but only 5-15% of primary lung adenocarcinomas...
  99. doi Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1
    H Gaude
    Centre de Recherche en Cancérologie de Lyon, INSERM U1052 CNRS UMR 5286, Lyon, France
    Oncogene 31:1582-91. 2012
    b>LKB1 is a tumor suppressor that is constitutionally mutated in a cancer-prone condition, called Peutz-Jeghers syndrome, as well as somatically inactivated in a sizeable fraction of lung and cervical neoplasms...
  100. doi Liver kinase B1 expression (LKB1) is repressed by estrogen receptor alpha (ERα) in MCF-7 human breast cancer cells
    Katja Linher-Melville
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
    Biochem Biophys Res Commun 417:1063-8. 2012
    Liver kinase 1 (LKB1) is emerging as a multifunctional protein, acting as a key metabolic enzyme, regulator of cell polarity, and transcription factor...

Research Grants62

  1. THE ROLE OF PEUTZ JEGHER GENE IN APOPTOSIS
    Junying Yuan; Fiscal Year: 2005
    ..appended verbatim from investigator's abstract): The objective of this proposal is to determine the mechanism of LKB1/STK11, a serine/threonine kinase, in mediating apoptosis...
  2. The role of LKB1 in the maintenance of genomic stability.
    Zhi Xiang Xu; Fiscal Year: 2013
    ..Inactivating mutations in LKB1 are also found in cancer patients without PJS, including sporadic lung adenocarcinoma (common), ovarian cancer, ..
  3. George Souroullas; Fiscal Year: 2014
    ..The LKB1 (Liver Kinase B1) gene, also known as serine threonine kinase 11 (STK11), was originally identified as the causative mutation ..
  4. MOUSE MODEL FOR THE PEUTZ JEGHERS SYNDROME
    Marsha Frazier; Fiscal Year: 2002
    ..PJS is caused by germline mutations in the gene encoding the serine threonine kinase LKB1. Recent evidence that the LKB1 gene is a tumor suppressor in hamartomas and adenocarcinomas from PJS patients...
  5. David J Kwiatkowski; Fiscal Year: 2016
    ..and Bannayan-Riley-Ruvalcaba syndrome, due to mutations in PTEN;and Peutz-Jeghers syndrome, due to mutations in LKB1. Genetically, these genes function in classic tumor suppressor gene fashion, with germline inactivation of a single ..
  6. A kinase pathway required for cortical neuron polarization
    Franck Polleux; Fiscal Year: 2012
    ..Using a candidate approach, we recently obtained preliminary results demonstrating that the serine/threonine kinase LKB1 (also known as Par4 or STK11) is required for polarization of cortical neurons in vivo (Barnes et al...
  7. Chemoprevention of Peutz-Jeghers Polyposis in a Mouse Model by Niclosamide
    Chongjuan Wei; Fiscal Year: 2012
    ..Germline mutations of the tumor suppressor gene LKB1 are responsible for most PJS cases...
  8. Shelley L Berger; Fiscal Year: 2016
    ..We also uncovered an unanticipated novel pathway in the nucleus, where LKB1, the Peutz=Jeager kinase, and its downstream target, AMPK, function as transcriptional coactivators for p53...
  9. ADSS1 inactivation as a promoter of tumor metabolism and lung carcinogenesis
    Christopher R Herzog; Fiscal Year: 2010
    ..By controlling cellular AMP levels, ADSS1 controls the activity of serine/threonine kinase 11 (STK11) (also LKB1), which is the apical kinase that regulates cell growth and survival during energy stress...
  10. JOSE M TEIXEIRA; Fiscal Year: 2016
    ..regulation of mTor gene expression and activity for comparison with other mutant mouse models lacking myometrial Lkb1, the gene mutated in patients with Peutz-Jeghers Syndrome, and Tsc1, both of which also induce mTor activity and ..
  11. The Role of STRADalpa in Corticogenesis and Neuropathogenesis of Pretzel Syndrome
    KSENIA ALEXANDRA ORLOVA; Fiscal Year: 2010
    ..Interestingly, mutations in LKBl give rise to Peutz-Jeghers syndrome (PJS), a distinct autosomal dominant disorder characterized by intestinal polyposis and increased cancer incidence...
  12. REUBEN JAMES SHAW; Fiscal Year: 2015
    ..Previously, the serine/threonine kinase LKB1 was identified as the critical upstream kinase mediating AMPK activation in most mammalian tissues...
  13. Mouse Model of Pancreatic Tumorigenesis with Dysregulation of mTOR
    Chongjuan Wei; Fiscal Year: 2009
    ..It is one of the most lethal cancers, with most patients dying within a year. LOH at the LKB1 locus is seen in approximately 32% of pancreatic tumors suggesting its involvement in pancreatic tumorigenesis...
  14. Exploring the Role of TAK1 in Neuronal Polarization
    MEGHAN LYNN MORGAN-SMITH; Fiscal Year: 2011
    ..At the core of this cascade is the phosphorylation of a serine/threonine kinase LKB1 on its Serine 431...
  15. Molecular genetics of epithelium formation in C. elegans
    Stephen E Von Stetina; Fiscal Year: 2010
    ..For example, the serine/threonine kinase LKB1 is sufficient to polarize single human intestine cells in the absence of cadherin-mediated signaling...
  16. Anthony P Barnes; Fiscal Year: 2016
    ..previously undertaken studies to identify genes controlling polarity during cortical development and established LKB1 (also called Par4), a serine-threonine kinase, as a key regulator of both axon-dendrite polarity and cell survival...
  17. Melanie A Samuel; Fiscal Year: 2014
    ..that these changes are accompanied by, and may result from, dysregulation of a specific serine/threonine kinase, LKB1. LKB1 is a central modulator of cellular metabolism and phosphorylates and activates the energy sensor AMPK...
  18. The Role of LKB1 in the Specification of Neuronal Polarity
    Anthony P Barnes; Fiscal Year: 2010
    ..One candidate molecule is LKB1 (also called Par4), a serine-threonine kinase that is a firmly established regulator of cell polarity in ..
  19. Interaction of Estrogen and AMPK in the Hypothalamus
    Jessica Healy; Fiscal Year: 2012
    ..energy sensing enzyme AMP-activated protein kinase (AMPK), which is phosphorylated (pAMPK) by the enzyme liver kinase B1 (LKB1) and activated when a decrease in the AMP:ATP ratio signals low endogenous energy...
  20. Mechanism of Metformin Action in Normal and PCOS Theca Cells
    Jan M McAllister; Fiscal Year: 2012
    ..An examination of the classical metformin activated LKB1/ AMP-activated protein kinase (AMPK) signaling cascade, provided the novel findings that LKB1 phosphorylation, as ..
  21. Jeffrey E Pessin; Fiscal Year: 2016
    ..complex, nuclear SREBP-1c stability, lipogenic gene expression and de novo lipogenesis in liver-specific Raptor and LKB1 knocout mice;2) determining the function of CDK8/CycC degradation-resistant mutants in mouse liver;and 3) analyzing ..
  22. AMPK Endothelial Cell Dysfunction and the Metabolic Syndrome (PROGRAM PROJECT)
    Neil B Ruderman; Fiscal Year: 2013
    ..cell as well as peripheral tissues and 2) that such dysregulation is the result of impairment of a SIRT1/LKB1 signaling mechanism that we have demonstrated regulates AMPK activity in various cultured cells and in the liver in ..
  23. REUBEN JAMES SHAW; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Cancer genetics has revealed that p53 and LKB1/STK11 are the most commonly mutated tumor suppressors in sporadic human non-small cell lung cancers (NSCLC), the leading source of annual cancer deaths ..
  24. Oxymax System with Teadmill for Quantifying Exercise in Mice
    Neil B Ruderman; Fiscal Year: 2012
    ..lab will use the Oxymax system with treadmills to examine the acute and chronic effects of exercise on the SIRT1/LKB1/AMPK/eNOS signaling mechanism that it has recently identified in the endothelium of the mouse aorta and is ..
  25. AMP-activated protein kinase in the ischemic heart
    Lawrence H Young; Fiscal Year: 2012
    ..the specific role of cardiomyocte-derived MIF during ischemia, 2) define the roles of the tumor suppressing kinase LKB1 and calcium calmodulin-activated protein kinase kinase (CaMKK2) in AMPK activation in the ischemic heart and 3) ..
  26. Regulation of LKB1 and AMPK Signaling by BRAF in Melanoma
    Bin Zheng; Fiscal Year: 2012
    ..The advisory committee and the vibrant scientific environment at the Columbia University Medical Center will facilitate Dr. Zheng in achieving his scientific and career goals. ..
  27. Adiponectin effects on leptin signaling in hepatocellular carcinoma
    Neeraj Kumar Saxena; Fiscal Year: 2011
    ..Adiponectin activates AMPK in an LKB1-dependent manner, and inhibits S6K activation demonstrating the involvement of LKB1-AMPK-S6K axis...
  28. Claire C Bastie; Fiscal Year: 2014
    ..nutrient-sensor system that regulates cellular and whole body energy homeostasis via AMPK and its upstream kinase, LKB1. In our published work (Bastie et. al. 2007 Cell Metab...
  29. Sir2 Regulates AMPK and Lipid Metabolism in Diabetes
    Mengwei Zang; Fiscal Year: 2012
    ..The energy sensor AMP-activated protein kinase (AMPK) and its upstream kinase, LKB1, have been implicated in the therapeutic effect of metformin, an anti-diabetic drug used worldwide...
  30. Jeffrey E Pessin; Fiscal Year: 2014
    ..We will also examine the interaction of these pathways with the LKB1/AMPK patiiway in mediating glucose uptake and GLUT4 translocation...
  31. SIRT1, AMPK , and hepatocyte nutrient sensing
    LAUREN NELSON DISE; Fiscal Year: 2012
    ..Aim 2 will explore the hypothesis that SIRT1 activates AMPK via modulation of the AMPK kinase LKB1 by assessing LKB1 deacetylation and activation in HepG2 cells incubated with known SIRT1 and AMPK activators...
  32. Exercise Regulation of Glucose Metabolism in Skeletal Muscle
    Laurie J Goodyear; Fiscal Year: 2012
    ..The tumor suppressor protein LKB1 has recently been identified as an upstream kinase for AMPK and 12 other AMPK-related proteins...
  33. David M Sabatini; Fiscal Year: 2016
    ..mTORC1 deregulation also occurs in cancer cells that have lost the PTEN, NF1, LKB1, or p53 tumor suppressors...
  34. Wei Zhou; Fiscal Year: 2015
    ..b>LKB1 is commonly known as a tumor suppressor because somatic LKB1 inactivation mutation is one of the most frequently ..
  35. Ian G Macara; Fiscal Year: 2015
    ..mammary stem cell maintenance, and that it functions through recruitment of the master kinase and polarity protein, LKB1. We found that Par3L, but not Par3, binds LKB1. Loss of Par3L reduces mammary gland regeneration efficiency...
  36. Richard G Moran; Fiscal Year: 2014
    Summary The majority of human cancers have lost the function of tumor suppressor genes (LKB1, PTEN, TSC1/2) controlling energy metabolism on the Akt-mTOR pathway or have hyperactivity of oncogenes (PI3kinase, Akt) on this same pathway...
  37. Mechanisms Regulating Functional Beta-cell Recovery
    Gordon P Meares; Fiscal Year: 2010
    ..the role of nitric oxide in cytokine-induced activation of AMPK;and the role of kinases upstream of AMPK such as LKB1 and CamKKp. 2...
  38. Michael A Teitell; Fiscal Year: 2015
    ..DNA double stranded breaks (DSBs) during IG class switch recombination (CSR) in GC B cells, signals through LKB1 to inactivate CRTC2, a known transcriptional co-activator of CREB...
  39. Energy Restrction and Mammary Cancer
    Henry J Thompson; Fiscal Year: 2013
    ..Since DER has direct effects, based on our ongoing work, on at least 4 tumor suppressor genes (LKB1, TSC2, PTEN, and p53) that are misregulated during the development of cancer, it is likely that work such as ours ..
  40. Shear Stress, AMPK, and Endothelial Functions
    JOHN Y_J SHYY; Fiscal Year: 2013
    ..e., calmodulin-dependent protein kinase kinase (CaMKK) and LKB1], which in turn activates AMPK...
  41. The Effect of Diet and Nutrients on the Progression and Treatment of Prostate Can
    George Thomas; Fiscal Year: 2013
    ..mTORCI signaling pathway, which is opposed by a large number of tumor suppressors including PTEN, TSC1/2, NF1, LKB1, 4E-BP1, PDCD4, and PML...
  42. Michael A Teitell; Fiscal Year: 2015
    ..DNA double-stranded breaks (DSBs) during IG class switch recombination (CSR) in GC B cells, signals through LKB1 to inactivate CRTC2, a known transcriptional co-activator of CREB...
  43. LKB1 tumor suppressor and human cancer
    Diego H Castrillon; Fiscal Year: 2013
    Recent work from our laboratories and others has shown that the LKB1 (STKII) tumor suppressor gene is frequently inactivated (through deletions or point mutations) in a wide variety of human cancers...
  44. Disparities in Breast Cancer: Development and Survival in Hispanic and NHW Women
    Martha L Slattery; Fiscal Year: 2013
    ..These genetic factors will be evaluated with survival to determine their contribution to survival differences observed for Hispanic and NHW women. ..
  45. Avtar K Singh; Fiscal Year: 2015
    ..In Specific Aim 3, we will determine whether GSNO-mediated nitrosylation of either AMPK or its upstream kinase LKB1 is responsible for the inhibition of aberrant eNOS activity and the reduced formation of peroxynitrite...
  46. Alec Kimmelman; Fiscal Year: 2015
    ..of >70 mouse and human PDAC lines to determine if various genotypes (combinations of KRAS, p53, Ink4a, Smad4, Lkb1, and PTEN mutations), global gene copy number and mRNA expression profiles can predict response to HCQ as a ..
  47. Henry J Thompson; Fiscal Year: 2016
    ..exerts effects systemically by reducing signaling via the insulin/IGF-1 pathway and intracellularly by activating LKB1/AMPK/raptor and SIRT1 signaling nodes and induces TSC1/2 repressor activity which counteract the effects of mTOR de-..
  48. mTOR signaling and sporadic chordomas
    Sangyeul Han; Fiscal Year: 2010
    ..In addition to TSC genes, other tumor suppressor genes such as PTEN, NF1 and LKB1 critically regulate mTOR signaling through TSC proteins...
  49. A Schizosaccharomyces pombe Model of Birt-Hogg-Dube Syndrome
    ELIZABETH HENSKE; Fiscal Year: 2007
    ..develop in patients with germline mutations in at least four other tumor suppressor genes (PTEN, TSC1, TSC2 and LKB1). Loss of the protein products of these genes results in activation of the kinase mTOR. The S...
  50. Steven R Grossman; Fiscal Year: 2016
    ..Among the genes dysregulated in NSCLC mutations in p53 and LKB1 are major traits, and their critical effect on lung carcinogenesis is supported by many mouse models...
  51. Translational Research in Polycystic Ovary Syndrome
    John E Nestler; Fiscal Year: 2012
    ..Strauss) with new resources for support of research;commitment to research (in particular in Women's Health), establishment of a CTSA, and the NIH Roadmap;and demonstrated success in increasing NIH funding. ..
  52. Nicholas C Denko; Fiscal Year: 2016
    ..We have organized this proposal into the following four specific aims. 1) Determine the role of tumor suppressor LKB1 in mediating the effect of biguanides on mitochondrial metabolism...
  53. KAYLA RENEE HILL; Fiscal Year: 2014
    ..a transient cellular energy depletion that blocks Akt pro-survival signaling and activates pro-apoptotic JNK via LKB1-dependent AMPK activation, leading to hair cell death...
  54. Targeting Cell Signaling in lung cancer to enhance therapeutic efficacy
    Fadlo Raja Khuri; Fiscal Year: 2012
    ..Project 2 targets LKB1, a tumor suppressor gene known to be inactivated or mutated in lung cancer, and its role as a key regulator of ..
  55. Dipali Sharma; Fiscal Year: 2014
    ..Adiponectin activates AMPK in an LKB1-dependent manner, and inhibits S6K activation demonstrating the involvement of LKB1-AMPK-S6K axis...
  56. KWOK KIN WONG; Fiscal Year: 2016
    ..de novo mouse lung cancer and melanoma models driven by activated oncogenic Kras and concurrent tumor suppressor Lkb1 loss that has a >60% penetrance of regional and distant metastases...
  57. Neil B Ruderman; Fiscal Year: 2015
    ..In the preceding grant period, we discovered that SIRT1 can activate AMPK by deacetylating its upstream kinase LKB1 and two other groups found that AMPK can activate SIRT1, suggesting the existence of a SIRT1/AMPK cycle...
  58. The role of adiponectin in hepatocelluar carcinoma
    Neeraj Kumar Saxena; Fiscal Year: 2010
    ..the growth and metastatic potential of hepatocellular carcinoma cells by increased crosstalk between AMPK and LKB1-TSC2-mTOR pathway...
  59. William Y Kim; Fiscal Year: 2014
    ..Recently, somatic mutations of the LKB1 tumor suppressor gene have been added to this list...
  60. Mentoring and Research in Mouse Models of Cancer and Infertility
    Diego H Castrillon; Fiscal Year: 2011
    ..We will study the recently discovered tumor suppressor Lkb1 in normal reproductive tract function and disease...
  61. EDWARD JAMES MILLER; Fiscal Year: 2015
    ..The immediate career goal of the investigator is to explore energetic signaling via AMPK-LKB1, cardiac metabolism, and cardiomyocyte biology in diabetic heart failure...
  62. Diego H Castrillon; Fiscal Year: 2014
    ..Specifically, we have demonstrated that inactivation of the LKB1 tumor suppressor drives the formation of highly invasive cancers in both mice and humans...