title: LKB1 controls human bronchial epithelial morphogenesis through p114RhoGEF-dependent RhoA activation.
abstract: LKB1 is a Ser/Thr kinase that plays an important role in controlling both energy metabolism and cell polarity in metazoan organisms. LKB1 is also a tumor suppressor, and homozygous, inactivating mutations are found in a wide range of human cancers. In lung cancer, inactivating mutations are found in 10 to 50% of cases, but the consequences of functional loss in this context are poorly understood. We report here that LKB1 is required for the maturation of apical junctions in the human bronchial epithelial cell line 16HBE14o- (16HBE). This activity is dependent on an interaction with the Rho guanine nucleotide exchange factor p114RhoGEF but is independent of LKB1 kinase activity. Together, LKB1 and p114RhoGEF control RhoA activity in these cells to promote apical junction assembly.
authors: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Xiaojian
authors: X
authors: Xu
authors: Dan
authors: D
authors: Jin
authors: Joanne
authors: J
authors: Durgan
authors: Alan
authors: A
authors: Hall
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000595:Amino Acid Sequence; D000818:Animals; D055745:Bronchioles / Q000166:cytology*; D002460:Cell Line; D048430:Cell Shape; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000502:physiology*; D064067:Rho Guanine Nucleotide Exchange Factors; D025521:Tumor Suppressor Proteins; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000097868:Polo-like Kinases
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D020662:Guanine Nucleotide Exchange Factors; D010446:Peptide Fragments; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors; D025521:Tumor Suppressor Proteins; D020742:rhoA GTP-Binding Protein; C577230:ARHGEF18 protein, human; C066737:RHOA protein, human; C486256:PLK3 protein, human; D000097868:Polo-like Kinases; C109790:STK11 protein, human
references: Oncogene. 2007 Dec 13;26(57):7825-32
references: 17599048
references: Nature. 2003 Jan 23;421(6921):379-84
references: 12540903
references: Nat Cell Biol. 2012 Aug;14(8):793-801
references: 22797597
references: Lung Cancer. 2010 Nov;70(2):136-45
references: 20207041
references: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17272-7
references: 17088526
references: Br J Cancer. 2008 Sep 2;99(5):683-8
references: 18728656
references: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):819-22
references: 17204563
references: Circ Res. 2003 Oct 31;93(9):848-56
references: 14512443
references: Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8941-6
references: 19443685
references: J Cell Biol. 2011 Oct 17;195(2):245-61
references: 22006950
references: BMC Cell Biol. 2010 Oct 12;11:77
references: 20939895
references: PLoS One. 2009;4(4):e5137
references: 19340305
references: Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18892-7
references: 20956321
references: Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):E388-97
references: 22308451
references: EMBO J. 2003 Oct 1;22(19):5102-14
references: 14517248
references: Cell Commun Signal. 2011 Oct 28;9(1):23
references: 22035226
references: Proc Natl Acad Sci U S A. 2012 May 8;109(19):7344-9
references: 22529391
references: Mol Biol Cell. 2010 Sep 1;21(17):2996-3006
references: 20631255
references: Hum Mol Genet. 2005 May 15;14(10):1283-92
references: 15800014
references: Nature. 2007 Aug 16;448(7155):807-10
references: 17676035
references: Nat Cell Biol. 2011 Feb;13(2):159-66
references: 21258369
references: Cancer Res. 2008 May 15;68(10):3562-5
references: 18483235
references: Curr Biol. 2011 Feb 22;21(4):259-69
references: 21276723
references: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9248-51
references: 10430928
references: Fam Cancer. 2011 Sep;10(3):447-53
references: 21516316
references: Cell. 2004 Feb 6;116(3):457-66
references: 15016379
references: Nature. 1998 Jan 8;391(6663):184-7
references: 9428765
references: Dev Cell. 2009 Apr;16(4):551-62
references: 19386264
references: EMBO J. 2003 Jun 16;22(12):3062-72
references: 12805220
references: Mol Endocrinol. 2007 Dec;21(12):3039-49
references: 17761947
references: Annu Rev Biochem. 2006;75:137-63
references: 16756488
references: Mol Cell. 2001 Jun;7(6):1307-19
references: 11430832
references: Acta Physiol (Oxf). 2009 May;196(1):65-80
references: 19245654
references: Clin Cancer Res. 2006 May 15;12(10):3209-15
references: 16707622
references: Biochem Biophys Res Commun. 1999 Aug 11;261(3):750-5
references: 10441497
references: Cancer Cell. 2010 Jun 15;17(6):547-59
references: 20541700
references: Development. 2000 Apr;127(7):1467-75
references: 10704392
references: J Cell Biol. 2012 Dec 24;199(7):1117-30
references: 23266956
references: Curr Biol. 2009 Jan 13;19(1):37-42
references: 19110428
references: Mol Cell Biol. 2011 Jan;31(1):81-91
references: 20974804
references: J Biol Chem. 2001 Jun 1;276(22):19469-82
references: 11297520
references: Mol Cell Biol. 2008 Apr;28(7):2414-25
references: 18227155
references: Cancer Res. 2006 Aug 15;66(16):7870-9
references: 16912160