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Role of Src-specific phosphorylation site on focal adhesion kinase for senescence-associated apoptosis resistance

Cited 21 time in Web of Science Cited 20 time in Scopus
Authors
Ryu, S. J.; Cho, K. A.; Oh, Y. S.; Park, S. C.
Issue Date
2006-03-09
Publisher
Springer Verlag
Citation
Apoptosis 2006; 11: 303-313
Keywords
Apoptosis/*physiologyCaspase 3/metabolism*Cell AgingCell CycleCells, CulturedCollagen Type XI/metabolismEnzyme ActivationEnzyme Inhibitors/pharmacologyFibroblasts/cytology/drug effects/physiologyFocal Adhesion Protein-Tyrosine Kinases/genetics/*metabolismHumansHydrogen Peroxide/pharmacologyOxidants/pharmacologyPhosphorylationRNA, Small Interfering/metabolismStaurosporine/pharmacologyTyrosine/metabolismsrc-Family Kinases/antagonists & inhibitors/*metabolism
Abstract
A decreased apoptotic response toward noxious stress is an issuing characteristic of the aging phenotype. Hydrogen peroxide or staurosporine induced apoptosis readily in young cells but not in senescent cells. We showed that focal adhesion kinase (FAK) expression and its phosphorylation at Tyr397, autophosphorylation site for focal adhesion formation, and Tyr577, Src-dependent phosphorylation site, were both increased in senescent cells. Moreover, FAK was inactivated proteolytically by apoptotic stimuli in young cells, but not in senescent cells. In addition, senescent cells whose FAK expression was downregulated by siRNA showed the increased level of apoptosis by staurosporine treatment via caspase-3 activation but not by hydrogen peroxide treatment. Interestingly dephosphorylation at Tyr577 of FAK by PP2 treatment, Src-family kinase inhibitor, induced the apoptosis by staurosporine in senescent cells but dephosphorylation at Tyr397 by downregulation of caveolin-1 was not affected. These data suggest that FAK might differently regulate apoptosis and focal adhesion formation through site-specific tyrosine phosphorylation in senescent cells.
ISSN
1360-8185 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16523241

http://hdl.handle.net/10371/24808
DOI
https://doi.org/10.1007/s10495-006-3978-9
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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