Document Detail

Transition between proliferation and differentiation for lens epithelial cells is regulated by Src family kinases.
MedLine Citation:
PMID:  12203728     Owner:  NLM     Status:  MEDLINE    
As in many cell types, lens cells must withdraw from the cell cycle before they initiate their differentiation. The involvement of Src family kinases (SFKs) in this key initiating event in cell differentiation was examined in lens epithelial cell cultures. SFK activity was suppressed with the specific inhibitor PP1. This induced expression of the cyclin-dependent kinase (CDK) inhibitors p27 and p57 and suppressed lens epithelial cell proliferation. Therefore, inhibition of SFK activity created conditions permissive for undifferentiated lens epithelial cells to withdraw from the cell cycle. Growth of the lens epithelial cell cultures in the presence of PP1 induced expression of filensin and CP49, lens differentiation-specific intermediate filament proteins, providing evidence that suppression of SFK activity also promoted the initiation of lens cell differentiation. The mechanism by which PP1 signaled cell cycle withdrawal and commitment to differentiation was shown to involve induction of N-cadherin cell-cell junction assembly and reorganization of the actin cytoskeleton from stress fibers to cortical filaments. This result was supported by the compaction of the epithelial monolayer in response to PP1, a morphogenetic change that we have previously shown to be dependent on N-cadherin function and a hallmark of the commencement of the lens differentiation program in culture. The results presented in this study suggest that the decision of lens epithelial cells to withdraw from the cell cycle and initiate differentiation requires inhibition of SFKs and the formation of N-cadherin cell-cell junctions.
Janice L Walker; Liping Zhang; A Sue Menko
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Developmental dynamics : an official publication of the American Association of Anatomists     Volume:  224     ISSN:  1058-8388     ISO Abbreviation:  Dev. Dyn.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-30     Completed Date:  2003-04-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9201927     Medline TA:  Dev Dyn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  361-72     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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MeSH Terms
Actins / metabolism
Cadherins / metabolism
Cell Cycle / physiology
Cell Cycle Proteins / metabolism
Cell Differentiation / physiology*
Cell Division / physiology*
Cells, Cultured
Chick Embryo
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinase Inhibitor p57
Enzyme Inhibitors / metabolism
Epithelial Cells / cytology,  physiology*
Eye Proteins / metabolism
Integrin alpha6 / metabolism
Intermediate Filament Proteins / metabolism
Lens, Crystalline / cytology*,  physiology
Nuclear Proteins / metabolism
Oncogene Protein pp60(v-src) / metabolism
Pyrazoles / metabolism
Pyrimidines / metabolism
Quail / embryology
Tumor Suppressor Proteins / metabolism
src-Family Kinases / antagonists & inhibitors,  metabolism*
Grant Support
Reg. No./Substance:
0/4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; 0/Actins; 0/Cadherins; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p57; 0/Enzyme Inhibitors; 0/Eye Proteins; 0/Integrin alpha6; 0/Intermediate Filament Proteins; 0/Nuclear Proteins; 0/Pyrazoles; 0/Pyrimidines; 0/Tumor Suppressor Proteins; 0/filensin; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC Protein pp60(v-src); EC Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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