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
Products:     LKB1

Top Publications

  1. Jenne D, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18:38-43 pubmed
    ..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. Nath Sain S, Marignani P. LKB1 catalytic activity contributes to estrogen receptor alpha signaling. Mol Biol Cell. 2009;20:2785-95 pubmed publisher
    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...
  3. Su G, Hruban R, Bansal R, Bova G, Tang D, Shekher M, et al. Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol. 1999;154:1835-40 pubmed
    ..It was recently shown that germline mutations of the STK11/LKB1 gene are responsible for PJS...
  4. Sapkota G, Deak M, Kieloch A, Morrice N, Goodarzi A, Smythe C, et al. Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated phosphorylation of LKB1/STK11 at Thr-366. Biochem J. 2002;368:507-16 pubmed
    The serine/threonine protein kinase LKB1 functions as a tumour suppressor, and mutations in this enzyme lead to the inherited Peutz-Jeghers cancer syndrome...
  5. Resta N, Giorda R, Bagnulo R, Beri S, Della Mina E, Stella A, et al. Breakpoint determination of 15 large deletions in Peutz-Jeghers subjects. Hum Genet. 2010;128:373-82 pubmed publisher
    ..STK11/LKB1 (hereafter named STK11) germline mutations account for the large majority of PJS cases whereas large deletions ..
  6. Kahn B, Alquier T, Carling D, Hardie D. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005;1:15-25 pubmed
    ..AMPK is regulated by upstream kinases of which the tumor suppressor, LKB1, is the first to be identified...
  7. Cheng H, Liu P, Wang Z, Zou L, Santiago S, Garbitt V, et al. SIK1 couples LKB1 to p53-dependent anoikis and suppresses metastasis. Sci Signal. 2009;2:ra35 pubmed publisher
    ..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 ..
  8. Nony P, Gaude H, Rossel M, Fournier L, Rouault J, Billaud M. Stability of the Peutz-Jeghers syndrome kinase LKB1 requires its binding to the molecular chaperones Hsp90/Cdc37. Oncogene. 2003;22:9165-75 pubmed
    ..Inactivating germline mutations of the LKB1 gene, which encodes a serine/threonine kinase, are responsible for the majority of PJS cases...
  9. ten Klooster J, Jansen M, Yuan J, Oorschot V, Begthel H, Di Giacomo V, et al. Mst4 and Ezrin induce brush borders downstream of the Lkb1/Strad/Mo25 polarization complex. Dev Cell. 2009;16:551-62 pubmed publisher
    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...

More Information

Publications108 found, 100 shown here

  1. Vasovcak P, Puchmajerova A, Roubalík J, Krepelova A. Mutations in STK11 gene in Czech Peutz-Jeghers patients. BMC Med Genet. 2009;10:69 pubmed publisher
    Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis...
  2. Marignani P, Kanai F, Carpenter C. LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest. J Biol Chem. 2001;276:32415-8 pubmed
    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...
  3. Jaleel M, McBride A, Lizcano J, Deak M, Toth R, Morrice N, et al. Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate. FEBS Lett. 2005;579:1417-23 pubmed
    Recent work has shown that the LKB1 tumour suppressor protein kinase phosphorylates and activates protein kinases belonging to the AMP activated kinase (AMPK) subfamily...
  4. Salloch H, Reinacher Schick A, Schulmann K, Pox C, Willert J, Tannapfel A, et al. Truncating mutations in Peutz-Jeghers syndrome are associated with more polyps, surgical interventions and cancers. Int J Colorectal Dis. 2010;25:97-107 pubmed publisher
    Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant polyposis syndrome caused by STK11 germline mutations. PJS is associated with an increased risk of cancer...
  5. Shinmura K, Goto M, Tao H, Shimizu S, Otsuki Y, Kobayashi H, et al. A novel STK11 germline mutation in two siblings with Peutz-Jeghers syndrome complicated by primary gastric cancer. Clin Genet. 2005;67:81-6 pubmed
    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...
  6. Alexander A, Walker C. The role of LKB1 and AMPK in cellular responses to stress and damage. FEBS Lett. 2011;585:952-7 pubmed publisher
    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...
  7. Karuman P, Gozani O, Odze R, Zhou X, Zhu H, Shaw R, et al. The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell. 2001;7:1307-19 pubmed
    Here, we investigate the mechanism and function of LKB1, a Ser/Thr kinase mutated in Peutz-Jegher syndrome (PJS). We demonstrate that LKB1 physically associates with p53 and regulates specific p53-dependent apoptosis pathways...
  8. Zhuang Z, Di G, Shen Z, Ding J, Shao Z. Enhanced expression of LKB1 in breast cancer cells attenuates angiogenesis, invasion, and metastatic potential. Mol Cancer Res. 2006;4:843-9 pubmed
    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...
  9. Volikos E, Robinson J, Aittomaki K, Mecklin J, Jarvinen H, Westerman A, et al. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J Med Genet. 2006;43:e18 pubmed
    b>LKB1/STK11 germline mutations cause Peutz-Jeghers syndrome (PJS)...
  10. Hemminki A, Tomlinson I, Markie D, Jarvinen H, Sistonen P, Björkqvist A, et al. Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nat Genet. 1997;15:87-90 pubmed
    ..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...
  11. Carretero J, Medina P, Blanco R, Smit L, Tang M, Roncador G, et al. Dysfunctional AMPK activity, signalling through mTOR and survival in response to energetic stress in LKB1-deficient lung cancer. Oncogene. 2007;26:1616-25 pubmed
    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...
  12. McCabe M, Powell D, Zhou W, Vertino P. Homozygous deletion of the STK11/LKB1 locus and the generation of novel fusion transcripts in cervical cancer cells. Cancer Genet Cytogenet. 2010;197:130-41 pubmed publisher
    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...
  13. Bignell G, Barfoot R, Seal S, Collins N, Warren W, Stratton M. Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer. Cancer Res. 1998;58:1384-6 pubmed
    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...
  14. Sapkota G, Boudeau J, Deak M, Kieloch A, Morrice N, Alessi D. 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. Biochem J. 2002;362:481-90 pubmed
    ..The causative gene encodes a nuclear-localized protein kinase, termed LKB1, which is predicted to function as a tumour suppressor...
  15. Lizcano J, Göransson O, Toth R, Deak M, Morrice N, Boudeau J, et al. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 2004;23:833-43 pubmed
    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)...
  16. Lim W, Olschwang S, Keller J, Westerman A, Menko F, Boardman L, et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology. 2004;126:1788-94 pubmed
    ..associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS). We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11...
  17. Sanchez Cespedes M, Parrella P, Esteller M, Nomoto S, Trink B, Engles J, et al. Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res. 2002;62:3659-62 pubmed
    ..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...
  18. Katajisto P, Vallenius T, Vaahtomeri K, Ekman N, Udd L, Tiainen M, et al. The LKB1 tumor suppressor kinase in human disease. Biochim Biophys Acta. 2007;1775:63-75 pubmed
    Inactivating germline mutations in the LKB1 gene underlie Peutz-Jeghers syndrome characterized by hamartomatous polyps and an elevated risk for cancer...
  19. Nafz J, De Castro Arce J, Fleig V, Patzelt A, Mazurek S, Rösl F. 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. Biochem J. 2007;403:501-10 pubmed
    ..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...
  20. Gaude H, Aznar N, Delay A, Brès A, Buchet Poyau K, Caillat C, et al. Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1. Oncogene. 2012;31:1582-91 pubmed publisher
    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...
  21. Nakagawa H, Koyama K, Miyoshi Y, Ando H, Baba S, Watatani M, et al. Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome. Hum Genet. 1998;103:168-72 pubmed
    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...
  22. Hastings M, Resta N, Traum D, Stella A, Guanti G, Krainer A. An LKB1 AT-AC intron mutation causes Peutz-Jeghers syndrome via splicing at noncanonical cryptic splice sites. Nat Struct Mol Biol. 2005;12:54-9 pubmed
    ..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-..
  23. Andrade Vieira R, Xu Z, Colp P, Marignani P. Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways. PLoS ONE. 2013;8:e56567 pubmed publisher
    The tumor suppressor kinase LKB1 is mutated in a broad range of cancers however, the role of LKB1 mammary gland tumorigenesis is not fully understood...
  24. Liang X, Wang P, Gao Q, Xiang T, Tao X. Endogenous LKB1 knockdown accelerates G(1)/S transition through p53 and p16 pathways. Cancer Biol Ther. 2010;9:156-60 pubmed
    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...
  25. De Rosa M, Galatola M, Quaglietta L, Miele E, De Palma G, Rossi G, et al. Alu-mediated genomic deletion of the serine/threonine protein kinase 11 (STK11) gene in Peutz-Jeghers syndrome. Gastroenterology. 2010;138:2558-60 pubmed publisher
  26. Amos C, Keitheri Cheteri M, Sabripour M, Wei C, McGarrity T, Seldin M, et al. Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet. 2004;41:327-33 pubmed
    Peutz-Jeghers syndrome (PJS) is a dominantly inherited disorder often caused by mutations in STK11...
  27. Hearle N, Rudd M, Lim W, Murday V, Lim A, Phillips R, et al. Exonic STK11 deletions are not a rare cause of Peutz-Jeghers syndrome. J Med Genet. 2006;43:e15 pubmed
    Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant cancer predisposition syndrome characterised by oro-facial pigmentation and hamartomatous polyposis of the gastrointestinal tract...
  28. Hezel A, Bardeesy N. LKB1; linking cell structure and tumor suppression. Oncogene. 2008;27:6908-19 pubmed publisher
    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...
  29. Ma Y, Zhang G, Fu X, Xia O, Zhan C, Li L, et al. Wnt signaling may be activated in a subset of Peutz-Jeghers syndrome polyps closely correlating to LKB1 expression. Oncol Rep. 2010;23:1569-76 pubmed
    ..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 ..
  30. Lin Marq N, Borel C, Antonarakis S. Peutz-Jeghers LKB1 mutants fail to activate GSK-3beta, preventing it from inhibiting Wnt signaling. Mol Genet Genomics. 2005;273:184-96 pubmed
    Peutz-Jeghers syndrome (PJS) is caused by germline mutations in the LKB1 gene, which encodes a serine-threonine kinase that regulates cell proliferation and polarity...
  31. Upadhyay S, Liu C, Chatterjee A, Hoque M, Kim M, Engles J, et al. LKB1/STK11 suppresses cyclooxygenase-2 induction and cellular invasion through PEA3 in lung cancer. Cancer Res. 2006;66:7870-9 pubmed
    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...
  32. Sanchez Cespedes M. A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome. Oncogene. 2007;26:7825-32 pubmed
    Germline LKB1 mutations are responsible for Peutz-Jeghers syndrome (PJS)...
  33. Stein S, Woods A, Jones N, Davison M, Carling D. The regulation of AMP-activated protein kinase by phosphorylation. Biochem J. 2000;345 Pt 3:437-43 pubmed
    ..Furthermore, we provide evidence that phosphorylation of Thr(172) may be involved in the sensitivity of the AMPK complex to AMP. ..
  34. Rossi D, Ylikorkala A, Korsisaari N, Salovaara R, Luukko K, Launonen V, et al. Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis. Proc Natl Acad Sci U S A. 2002;99:12327-32 pubmed
    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...
  35. Qiu W, Schönleben F, Thaker H, Goggins M, Su G. A novel mutation of STK11/LKB1 gene leads to the loss of cell growth inhibition in head and neck squamous cell carcinoma. Oncogene. 2006;25:2937-42 pubmed
    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 ..
  36. Fernandez P, Carretero J, Medina P, Jimenez A, Rodriguez Perales S, Paz M, et al. Distinctive gene expression of human lung adenocarcinomas carrying LKB1 mutations. Oncogene. 2004;23:5084-91 pubmed
    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 ..
  37. Kam M, Massare J, Gallinger S, Kinzie J, Weaver D, Dingell J, et al. Peutz-Jeghers syndrome diagnosed in a schizophrenic patient with a large deletion in the STK11 gene. Dig Dis Sci. 2006;51:1567-70 pubmed
  38. Morton J, Jamieson N, Karim S, Athineos D, Ridgway R, Nixon C, et al. LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology. 2010;139:586-97, 597.e1-6 pubmed publisher
    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...
  39. Spicer J, Rayter S, Young N, Elliott R, Ashworth A, Smith D. Regulation of the Wnt signalling component PAR1A by the Peutz-Jeghers syndrome kinase LKB1. Oncogene. 2003;22:4752-6 pubmed
    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...
  40. Chow E, Meldrum C, Crooks R, Macrae F, Spigelman A, Scott R. An updated mutation spectrum in an Australian series of PJS patients provides further evidence for only one gene locus. Clin Genet. 2006;70:409-14 pubmed
    The genetic predisposition Peutz-Jeghers Syndrome (PJS) has been shown to be associated with mutations in the serine threonine kinase 11 (STK11) gene but only a proportion of probands have been shown to harbour changes in the gene...
  41. Noga A, Soltys C, Barr A, Kovacic S, Lopaschuk G, Dyck J. Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy. Am J Physiol Heart Circ Physiol. 2007;292:H1460-9 pubmed
    AMP-activated protein kinase (AMPK) is a major metabolic regulator in the cardiac myocyte. Recently, LKB1 was identified as a kinase that regulates AMPK...
  42. Fan D, Ma C, Zhang H. The molecular mechanisms that underlie the tumor suppressor function of LKB1. Acta Biochim Biophys Sin (Shanghai). 2009;41:97-107 pubmed
    Germline mutations of the LKB1 tumor suppressor gene result in Peutz-Jeghers syndrome (PJS) characterized by intestinal hamartomas and increased incidence of epithelial cancers...
  43. Gu Y, Lin S, Li J, Nakagawa H, Chen Z, Jin B, et al. Altered LKB1/CREB-regulated transcription co-activator (CRTC) signaling axis promotes esophageal cancer cell migration and invasion. Oncogene. 2012;31:469-79 pubmed publisher
    b>LKB1 is a tumor susceptibility gene for the Peutz-Jeghers cancer syndrome and is a target for mutational inactivation in sporadic human malignancies...
  44. Hawley S, Boudeau J, Reid J, Mustard K, Udd L, Makela T, et al. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol. 2003;2:28 pubmed publisher
    ..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...
  45. Westerman A, Entius M, Boor P, Koole R, de Baar E, Offerhaus G, et al. Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families. Hum Mutat. 1999;13:476-81 pubmed
    ..The recently identified LKB1/STK11 gene located at chromosome 19p13.3 is mutated in a number of PJS pedigrees...
  46. Baas A, Boudeau J, Sapkota G, Smit L, Medema R, Morrice N, et al. Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. EMBO J. 2003;22:3062-72 pubmed
    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...
  47. Xie Z, Dong Y, Zhang M, Cui M, Cohen R, Riek U, et al. Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells. J Biol Chem. 2006;281:6366-75 pubmed
    ..In contrast, ONOO- activated PKCzeta in LKB1-deficient HeLa-S3 but affected neither AMPK-Thr172 nor AMPK activity...
  48. Katajisto P, Vaahtomeri K, Ekman N, Ventelä E, Ristimaki A, Bardeesy N, et al. LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis. Nat Genet. 2008;40:455-9 pubmed publisher
    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...
  49. Vaahtomeri K, Makela T. Molecular mechanisms of tumor suppression by LKB1. FEBS Lett. 2011;585:944-51 pubmed publisher
    The LKB1 tumor suppressor gene is frequently mutated in sporadic lung adenocarcinomas and cervical cancers and germline mutations are causative for Peutz-Jeghers syndrome characterized by gastrointestinal polyposis...
  50. Gill R, Yang S, Meerzaman D, Mechanic L, Bowman E, Jeon H, et al. Frequent homozygous deletion of the LKB1/STK11 gene in non-small cell lung cancer. Oncogene. 2011;30:3784-91 pubmed publisher
    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...
  51. Boudeau J, Baas A, Deak M, Morrice N, Kieloch A, Schutkowski M, et al. MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. EMBO J. 2003;22:5102-14 pubmed
    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...
  52. Boudeau J, Scott J, Resta N, Deak M, Kieloch A, Komander D, et al. Analysis of the LKB1-STRAD-MO25 complex. J Cell Sci. 2004;117:6365-75 pubmed
    Mutations in the LKB1 tumour suppressor threonine kinase cause the inherited Peutz-Jeghers cancer syndrome and are also observed in some sporadic cancers...
  53. Jaleel M, Villa F, Deak M, Toth R, Prescott A, van Aalten D, et al. The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation. Biochem J. 2006;394:545-55 pubmed
    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)...
  54. Ji H, Ramsey M, Hayes D, Fan C, McNamara K, Kozlowski P, et al. LKB1 modulates lung cancer differentiation and metastasis. Nature. 2007;448:807-10 pubmed
    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...
  55. Amin R, Hiroshima K, Iyoda A, Hoshi K, Honma K, Kuroki M, et al. LKB1 protein expression in neuroendocrine tumors of the lung. Pathol Int. 2008;58:84-8 pubmed publisher
    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...
  56. Dorfman J, Macara I. STRADalpha regulates LKB1 localization by blocking access to importin-alpha, and by association with Crm1 and exportin-7. Mol Biol Cell. 2008;19:1614-26 pubmed publisher
    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...
  57. Shah U, Sharpless N, Hayes D. LKB1 and lung cancer: more than the usual suspects. Cancer Res. 2008;68:3562-5 pubmed publisher
    ..For LKB1, a more recently identified human tumor suppressor gene, however, the problem is different...
  58. Zhong D, Liu X, Khuri F, Sun S, Vertino P, Zhou W. LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins. Cancer Res. 2008;68:7270-7 pubmed publisher
    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...
  59. Zeqiraj E, Filippi B, Goldie S, Navratilova I, Boudeau J, Deak M, et al. ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor. PLoS Biol. 2009;7:e1000126 pubmed publisher
    ..The pseudokinase STRAD activates the LKB1 tumour suppressor by forming a heterotrimeric complex with LKB1 and the scaffolding protein MO25...
  60. Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet. 1998;63:1641-50 pubmed
    ..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...
  61. Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo C, et al. STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol. 2001;159:2017-22 pubmed
    ..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 ..
  62. Smith D, Rayter S, Niederlander C, Spicer J, Jones C, Ashworth A. LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1. Hum Mol Genet. 2001;10:2869-77 pubmed
    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...
  63. Qanungo S, Haldar S, Basu A. Restoration of silenced Peutz-Jeghers syndrome gene, LKB1, induces apoptosis in pancreatic carcinoma cells. Neoplasia. 2003;5:367-74 pubmed publisher
    Germ line mutations of the LKB1 tumor suppressor gene lead to Peutz-Jeghers syndrome (PJS) with a predisposition to cancer...
  64. Setogawa T, Shinozaki Yabana S, Masuda T, Matsuura K, Akiyama T. The tumor suppressor LKB1 induces p21 expression in collaboration with LMO4, GATA-6, and Ldb1. Biochem Biophys Res Commun. 2006;343:1186-90 pubmed
    The LKB1/STK11 serine/threonine kinase is mutated in Peutz-Jeghers syndrome and various sporadic cancers such as lung adenocarcinoma...
  65. Zeng P, Berger S. LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activation. Cancer Res. 2006;66:10701-8 pubmed
    The tumor suppressor LKB1 is an evolutionarily conserved serine/threonine kinase...
  66. Matsumoto S, Iwakawa R, Takahashi K, Kohno T, Nakanishi Y, Matsuno Y, et al. Prevalence and specificity of LKB1 genetic alterations in lung cancers. Oncogene. 2007;26:5911-8 pubmed
    Germline LKB1 mutations cause Peutz-Jeghers syndrome, a hereditary disorder that predisposes to gastrointestinal hamartomatous polyposis and several types of malignant tumors...
  67. Linher Melville K, Zantinge S, Singh G. Liver kinase B1 expression (LKB1) is repressed by estrogen receptor alpha (ER?) in MCF-7 human breast cancer cells. Biochem Biophys Res Commun. 2012;417:1063-8 pubmed publisher
    Liver kinase 1 (LKB1) is emerging as a multifunctional protein, acting as a key metabolic enzyme, regulator of cell polarity, and transcription factor...
  68. Sapkota G, Kieloch A, Lizcano J, Lain S, Arthur J, Williams M, et al. 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. J Biol Chem. 2001;276:19469-82 pubmed
    ..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...
  69. Boudeau J, Kieloch A, Alessi D, Stella A, Guanti G, Resta N. Functional analysis of LKB1/STK11 mutants and two aberrant isoforms found in Peutz-Jeghers Syndrome patients. Hum Mutat. 2003;21:172 pubmed
    ..PJS) is thought to be caused by mutations occurring in the widely expressed serine/threonine protein kinase named LKB1/STK11...
  70. Ghaffar H, Sahin F, Sanchez Cepedes M, Su G, Zahurak M, Sidransky D, et al. LKB1 protein expression in the evolution of glandular neoplasia of the lung. Clin Cancer Res. 2003;9:2998-3003 pubmed
    About one-third of sporadic lung adenocarcinomas demonstrates biallelic inactivation of the LKB1 gene, but the timing of this event is not known...
  71. Corradetti M, Inoki K, Bardeesy N, Depinho R, Guan K. Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev. 2004;18:1533-8 pubmed
    ..Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC...
  72. Aretz S, Stienen D, Uhlhaas S, Loff S, Back W, Pagenstecher C, et al. High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat. 2005;26:513-9 pubmed
    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...
  73. Legro R, Barnhart H, Schlaff W, Carr B, Diamond M, Carson S, et al. Ovulatory response to treatment of polycystic ovary syndrome is associated with a polymorphism in the STK11 gene. J Clin Endocrinol Metab. 2008;93:792-800 pubmed
    ..We found that the C allele of a single nucleotide polymorphism in the STK11 gene (expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin...
  74. Godlewski J, Nowicki M, Bronisz A, Nuovo G, Palatini J, De Lay M, et al. MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell. 2010;37:620-32 pubmed publisher
    ..The effects of miR-451 are mediated by LKB1, which it represses through targeting its binding partner, CAB39 (MO25 alpha)...
  75. Lützner N, De Castro Arce J, Rösl F. Gene expression of the tumour suppressor LKB1 is mediated by Sp1, NF-Y and FOXO transcription factors. PLoS ONE. 2012;7:e32590 pubmed publisher
    The serine/threonine kinase LKB1 is a tumour suppressor that regulates multiple biological pathways, including cell cycle control, cell polarity and energy metabolism by direct phosphorylation of 14 different AMP-activated protein kinase (..
  76. Resta N, Pierannunzio D, Lenato G, Stella A, Capocaccia R, Bagnulo R, et al. Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study. Dig Liver Dis. 2013;45:606-11 pubmed publisher
    Germline mutations in the STK11/LKB1 gene cause Peutz-Jeghers syndrome, an autosomal-dominantly inherited condition characterized by mucocutaneous pigmentation, hamartomatous gastrointestinal polyposis, and an increased risk for various ..
  77. Collins S, Reoma J, Gamm D, Uhler M. LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and prenylated in vivo. Biochem J. 2000;345 Pt 3:673-80 pubmed
    ..The human LKB1 (hLKB1) gene encodes a serine/threonine protein kinase that is deficient in the majority of patients with PJS...
  78. Shaw R, Kosmatka M, Bardeesy N, Hurley R, Witters L, Depinho R, et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A. 2004;101:3329-35 pubmed
    ..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 ..
  79. Kojima Y, Miyoshi H, Clevers H, Oshima M, Aoki M, Taketo M. Suppression of tubulin polymerization by the LKB1-microtubule-associated protein/microtubule affinity-regulating kinase signaling. J Biol Chem. 2007;282:23532-40 pubmed
    b>LKB1, a tumor suppressor gene mutated in the Peutz-Jeghers syndrome, encodes a serine/threonine protein kinase...
  80. Koivunen J, Kim J, Lee J, Rogers A, Park J, Zhao X, et al. Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients. Br J Cancer. 2008;99:245-52 pubmed publisher
    Somatic mutations of LKB1 tumour suppressor gene have been detected in human cancers including non-small cell lung cancer (NSCLC)...
  81. Wingo S, Gallardo T, Akbay E, Liang M, Contreras C, Boren T, et al. Somatic LKB1 mutations promote cervical cancer progression. PLoS ONE. 2009;4:e5137 pubmed publisher
    ..Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor...
  82. Zeqiraj E, Filippi B, Deak M, Alessi D, van Aalten D. Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation. Science. 2009;326:1707-11 pubmed publisher
    The LKB1 tumor suppressor is a protein kinase that controls the activity of adenosine monophosphate-activated protein kinase (AMPK)...
  83. Komiya T, Coxon A, Park Y, Chen W, Zajac Kaye M, Meltzer P, et al. Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer. Oncogene. 2010;29:1672-80 pubmed publisher
    ..As LKB1 is a target for mutational inactivation in lung cancer and was recently shown to regulate hepatic Crtc2/CREB ..
  84. Feng Y, Wang Y, Wang Z, Fang Z, Li F, Gao Y, et al. The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss. Cancer Res. 2012;72:6502-11 pubmed publisher
    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...
  85. Guldberg P, thor Straten P, Ahrenkiel V, Seremet T, Kirkin A, Zeuthen J. Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma. Oncogene. 1999;18:1777-80 pubmed
    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...
  86. Boudeau J, Deak M, Lawlor M, Morrice N, Alessi D. Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability. Biochem J. 2003;370:849-57 pubmed
    b>LKB1 is a widely expressed serine/threonine protein kinase that is mutated in the inherited Peutz-Jeghers cancer syndrome...
  87. Mehenni H, Lin Marq N, Buchet Poyau K, Reymond A, Collart M, Picard D, et al. LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. Hum Mol Genet. 2005;14:2209-19 pubmed
    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...
  88. Wagner T, Mullally J, Fitzpatrick F. 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 tran. J Biol Chem. 2006;281:2598-604 pubmed
    b>LKB1, a unique serine/threonine kinase tumor suppressor, modulates anabolic and catabolic homeostasis, cell proliferation, and organ polarity. Chemically reactive lipids, e.g...
  89. Wang J, Imai Y, Lu B. Activation of PAR-1 kinase and stimulation of tau phosphorylation by diverse signals require the tumor suppressor protein LKB1. J Neurosci. 2007;27:574-81 pubmed
    ..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...
  90. Scott K, Nath Sain S, Agnew M, Marignani P. LKB1 catalytically deficient mutants enhance cyclin D1 expression. Cancer Res. 2007;67:5622-7 pubmed
    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...
  91. Zhang S, Schafer Hales K, Khuri F, Zhou W, Vertino P, Marcus A. The tumor suppressor LKB1 regulates lung cancer cell polarity by mediating cdc42 recruitment and activity. Cancer Res. 2008;68:740-8 pubmed publisher
    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...
  92. Lan F, Cacicedo J, Ruderman N, Ido Y. SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation. J Biol Chem. 2008;283:27628-35 pubmed publisher
    ..We examined whether a mechanistic connection exists between these molecules that involves the major AMPK kinase LKB1. Initial studies demonstrated that LKB1 is acetylated in cultured (HEK293T) cells, mouse white adipose tissue, and ..