LKB1 controls human bronchial epithelial morphogenesis through p114RhoGEF-dependent RhoA activation

Mol Cell Biol. 2013 Jul;33(14):2671-82. doi: 10.1128/MCB.00154-13. Epub 2013 May 6.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Amino Acid Sequence
  • Animals
  • Bronchioles / cytology*
  • Cell Line
  • Cell Shape
  • Enzyme Activation
  • Gene Knockdown Techniques
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Intercellular Junctions / metabolism
  • Mice
  • Morphogenesis
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Serine-Threonine Kinases / physiology*
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Respiratory Mucosa / physiology*
  • Rho Guanine Nucleotide Exchange Factors
  • Tumor Suppressor Proteins
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • ARHGEF18 protein, human
  • Guanine Nucleotide Exchange Factors
  • Peptide Fragments
  • RNA, Small Interfering
  • Rho Guanine Nucleotide Exchange Factors
  • Tumor Suppressor Proteins
  • RHOA protein, human
  • PLK3 protein, human
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases
  • rhoA GTP-Binding Protein