Document Detail


Focal adhesion kinase modulates cell adhesion strengthening via integrin activation.
MedLine Citation:
PMID:  19297531     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Focal adhesion kinase (FAK) is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and mechanosensing. Using FAK-null cells expressing FAK under an inducible promoter, we demonstrate that FAK regulates the time-dependent generation of adhesive forces. During the early stages of adhesion, FAK expression in FAK-null cells enhances integrin activation to promote integrin binding and, hence, the adhesion strengthening rate. Importantly, FAK expression regulated integrin activation, and talin was required for the FAK-dependent effects. A role for FAK in integrin activation was confirmed in human fibroblasts with knocked-down FAK expression. The FAK autophosphorylation Y397 site was required for the enhancements in adhesion strengthening and integrin-binding responses. This work demonstrates a novel role for FAK in integrin activation and the time-dependent generation of cell-ECM forces.
Authors:
Kristin E Michael; David W Dumbauld; Kellie L Burns; Steven K Hanks; Andrés J García
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-03-18
Journal Detail:
Title:  Molecular biology of the cell     Volume:  20     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-01     Completed Date:  2009-07-20     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2508-19     Citation Subset:  IM    
Affiliation:
Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biomechanics / drug effects
Cell Adhesion / drug effects
Fibroblasts / cytology*,  drug effects,  enzymology*
Fibronectins / metabolism
Focal Adhesion Protein-Tyrosine Kinases / metabolism*
Gene Knockdown Techniques
Humans
Integrin alpha5beta1 / metabolism*
Integrins / metabolism*
Kinetics
Mice
Phosphorylation / drug effects
Phosphotyrosine / metabolism
Protein Binding / drug effects
Solubility / drug effects
Talin / metabolism
Tetracycline / pharmacology
Vinculin / metabolism
Grant Support
ID/Acronym/Agency:
R01 GM065918-09/GM/NIGMS NIH HHS; R01-GM049882/GM/NIGMS NIH HHS; R01-GM065918/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Integrin alpha5beta1; 0/Integrins; 0/Talin; 125361-02-6/Vinculin; 21820-51-9/Phosphotyrosine; 60-54-8/Tetracycline; EC 2.7.10.2/Focal Adhesion Protein-Tyrosine Kinases
Comments/Corrections

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


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