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

Apoptosis : an International Journal on Programmed Cell Death
S J RyuSang Chul Park

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.

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Citations

Jan 27, 2009·Apoptosis : an International Journal on Programmed Cell Death·M Cecilia CainoMarcelo G Kazanietz
Dec 15, 2010·Pigment Cell & Melanoma Research·Sandy GiulianoCorine Bertolotto
Apr 2, 2009·Expert Opinion on Therapeutic Targets·Sung Jin Ryu, Sang Chul Park
Feb 27, 2008·International Journal of Radiation Biology·Maria Shatz, Mordechai Liscovitch
Sep 29, 2009·Mechanisms of Ageing and Development·Guorong LiPedro Gonzalez
Oct 5, 2007·The Journal of Investigative Dermatology·Nina S FunaJack L Arbiser
May 28, 2009·Cell Biochemistry and Function·Hong-Joo AnSang-Chul Park
Nov 12, 2009·Biochemical and Biophysical Research Communications·Sung Young KimSang Chul Park
Jun 3, 2017·Experimental & Molecular Medicine·Sang Chul Park
Mar 1, 2007·The Journal of Biological Chemistry·Elizabeth A BeierleVita M Golubovskaya
Jul 1, 2021·Experimental & Molecular Medicine·Ji-Hwan ParkSang Chul Park

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