TY - JOUR
T1 - Fas activation induces renal tubular epithelial cell ß8 integrin expression and function in the absence of apoptosis
AU - Jarad, George
AU - Wang, Bingcheng
AU - Khan, Shenaz
AU - DeVore, Jay
AU - Miao, Hui
AU - Wu, Karen
AU - Nishimura, Stephen L.
AU - Wible, Barbara A.
AU - Konieczkowski, Martha
AU - Sedor, John R.
AU - Schelling, Jeffrey R.
PY - 2002/12/6
Y1 - 2002/12/6
N2 - Cell fate following Fas (CD95) ligand or agonistic anti-Fas antibody stimulation is determined by multiple factors, including Fas expression level, microdomain localization, and modulating cytokines. Highly expressed Fas clusters and activates a canonical apoptosis signaling pathway. In less susceptible cells, Fas transduces apoptosis-independent signals, which are not well defined, but have been linked to inflammation, angiogenesis, and fibrosis. To identify apoptosis-independent Fas pathways, cultured renal tubular epithelial cells were stimulated with agonistic anti-Fas antibodies under conditions that did not cause cell death. Analysis of filter cDNA microarrays revealed β8 integrin subunit mRNA induction in Fasstimulated cells. β8 integrin mRNA expression increased within 3-6 h of Fas ligation due to enhanced mRNA stabilization, and mRNA increases were sustained for 48-72 h. Expression of plasma membrane β8 integrin, as well as its heterodimer partner αv, was increased by Fas activation with a similar kinetic pattern. Fas-induced αvβ8 expression correlated with increased migration to vitronectin, the ligand for αvβ8. Results from studies with function-blocking antibodies against other αvβ integrins or suppression β8 integrin expression by RNA interference demonstrated that induced β8 integrin expression mediated Fas-stimulated migration. We conclude that αvβ8 integrin induction defines an unexpected role for Fas in cell migration, rather than as a cell death receptor.
AB - Cell fate following Fas (CD95) ligand or agonistic anti-Fas antibody stimulation is determined by multiple factors, including Fas expression level, microdomain localization, and modulating cytokines. Highly expressed Fas clusters and activates a canonical apoptosis signaling pathway. In less susceptible cells, Fas transduces apoptosis-independent signals, which are not well defined, but have been linked to inflammation, angiogenesis, and fibrosis. To identify apoptosis-independent Fas pathways, cultured renal tubular epithelial cells were stimulated with agonistic anti-Fas antibodies under conditions that did not cause cell death. Analysis of filter cDNA microarrays revealed β8 integrin subunit mRNA induction in Fasstimulated cells. β8 integrin mRNA expression increased within 3-6 h of Fas ligation due to enhanced mRNA stabilization, and mRNA increases were sustained for 48-72 h. Expression of plasma membrane β8 integrin, as well as its heterodimer partner αv, was increased by Fas activation with a similar kinetic pattern. Fas-induced αvβ8 expression correlated with increased migration to vitronectin, the ligand for αvβ8. Results from studies with function-blocking antibodies against other αvβ integrins or suppression β8 integrin expression by RNA interference demonstrated that induced β8 integrin expression mediated Fas-stimulated migration. We conclude that αvβ8 integrin induction defines an unexpected role for Fas in cell migration, rather than as a cell death receptor.
UR - http://www.scopus.com/inward/record.url?scp=0037033011&partnerID=8YFLogxK
U2 - 10.1074/jbc.M204901200
DO - 10.1074/jbc.M204901200
M3 - Article
C2 - 12324452
AN - SCOPUS:0037033011
SN - 0021-9258
VL - 277
SP - 47826
EP - 47833
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 49
ER -