Document Detail


The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells.
MedLine Citation:
PMID:  20974804     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rho GTPases regulate multiple signaling pathways to control a number of cellular processes during epithelial morphogenesis. To investigate the downstream pathways through which Rho regulates epithelial apical junction formation, we screened a small interfering RNA (siRNA) library targeting 28 known Rho target proteins in 16HBE human bronchial epithelial cells. This led to the identification of the serine-threonine kinase PRK2 (protein kinase C-related kinase 2, also called PKN2). Depletion of PRK2 does not block the initial formation of primordial junctions at nascent cell-cell contacts but does prevent their maturation into apical junctions. PRK2 is recruited to primordial junctions, and this localization depends on its C2-like domain. Rho binding is essential for PRK2 function and also facilitates PRK2 recruitment to junctions. Kinase-dead PRK2 acts as a dominant-negative mutant and prevents apical junction formation. We conclude that PRK2 is recruited to nascent cell-cell contacts through its C2-like and Rho-binding domains and promotes junctional maturation through a kinase-dependent pathway.
Authors:
Sean W Wallace; Ana Magalhaes; Alan Hall
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-25
Journal Detail:
Title:  Molecular and cellular biology     Volume:  31     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-01-27     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  81-91     Citation Subset:  IM    
Affiliation:
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1274 York Ave., New York, NY 10065, USA.
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MeSH Terms
Descriptor/Qualifier:
Bronchi / cytology,  metabolism
Cell Line
Epithelial Cells / cytology,  metabolism
Humans
Intercellular Junctions / metabolism*
Protein Kinase C / antagonists & inhibitors,  chemistry,  genetics,  metabolism*
Protein Structure, Tertiary
RNA, Small Interfering / genetics
Signal Transduction
rho GTP-Binding Proteins / antagonists & inhibitors,  genetics,  metabolism*
rhoA GTP-Binding Protein / antagonists & inhibitors,  genetics,  metabolism
Grant Support
ID/Acronym/Agency:
GM081435/GM/NIGMS NIH HHS; //Medical Research Council
Chemical
Reg. No./Substance:
0/RHOC protein, human; 0/RNA, Small Interfering; 124671-05-2/RHOA protein, human; EC 2.7.1.-/protein kinase N; EC 2.7.11.13/Protein Kinase C; EC 3.6.5.2/rho GTP-Binding Proteins; EC 3.6.5.2/rhoA GTP-Binding Protein
Comments/Corrections

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