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LKB1 controls human bronchial epithelial morphogenesis through p114RhoGEF-dependent RhoA activation.
Xiaojian Xu, Dan Jin, Joanne Durgan, Alan Hall
Molecular and cellular biology 2013 Jul
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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.
Citation
Xiaojian Xu, Dan Jin, Joanne Durgan, Alan Hall.
LKB1 controls human bronchial epithelial morphogenesis through p114RhoGEF-dependent RhoA activation.
Molecular and cellular biology.
2013 Jul;33(14):2671-82
Mesh Tags
Amino Acid Sequence
Animals
Bronchioles
Cell Line
Cell Shape
Enzyme Activation
Gene Knockdown Techniques
Guanine Nucleotide Exchange Factors
Humans
Intercellular Junctions
Mice
Morphogenesis
Peptide Fragments
Phosphorylation
Protein Binding
Protein Interaction Domains and Motifs
Protein Interaction Mapping
Protein Processing, Post-Translational
Protein Transport
Protein-Serine-Threonine Kinases
RNA, Small Interfering
Respiratory Mucosa
Rho Guanine Nucleotide Exchange Factors
rhoA GTP-Binding Protein
Substances
ARHGEF18 protein, human
Guanine Nucleotide Exchange Factors
Peptide Fragments
RNA, Small Interfering
Rho Guanine Nucleotide Exchange Factors
RHOA protein, human
PLK3 protein, human
STK11 protein, human
Protein-Serine-Threonine Kinases
rhoA GTP-Binding Protein
PMID: 23648482
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