Role of Src-specific phosphorylation site on focal adhesion kinase for senescence-associated apoptosis resistance.
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.
Ryu
S J
SJ
Department of Biochemistry and Molecular Biology, The Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul, S. Korea.
Cho
K A
KA
Oh
Y S
YS
Park
S C
SC
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D016922:Cellular Senescence; D024161:Collagen Type XI / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D004791:Enzyme Inhibitors; D016877:Oxidants; D034741:RNA, Small Interfering; D014443:Tyrosine; D006861:Hydrogen Peroxide; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D053148:Caspase 3; D019311:Staurosporine