Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B
<p>Abstract</p> <p>Background</p> <p>Although the peptidyl-prolyl isomerase, cyclophilin-A (peptidyl-prolyl isomerase, PPIA), has been studied for decades in the context of its intracellular functions, its extracellular roles as a major contributor to both inflammation...
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doaj-fb4651253eaf4444b254090a1b5522232020-11-25T02:50:23ZengBMCCancer Cell International1475-28672012-07-011211910.1186/1475-2867-12-19Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa BBahmed KarimHenry CurtisHolliday MichaelRedzic JasminaCiobanu MadalinaZhang FengliWeekes ColinSclafani RobertDeGregori JamesEisenmesser Elan<p>Abstract</p> <p>Background</p> <p>Although the peptidyl-prolyl isomerase, cyclophilin-A (peptidyl-prolyl isomerase, PPIA), has been studied for decades in the context of its intracellular functions, its extracellular roles as a major contributor to both inflammation and multiple cancers have more recently emerged. A wide range of activities have been ascribed to extracellular PPIA that include induction of cytokine and matrix metalloproteinase (MMP) secretion, which potentially underlie its roles in inflammation and tumorigenesis. However, there have been conflicting reports as to which particular signaling events are under extracellular PPIA regulation, which may be due to either cell-dependent responses and/or the use of commercial preparations recently shown to be highly impure.</p> <p>Methods</p> <p>We have produced and validated the purity of recombinant PPIA in order to subject it to a comparative analysis between different cell types. Specifically, we have used a combination of multiple methods such as luciferase reporter screens, translocation assays, phosphorylation assays, and nuclear magnetic resonance to compare extracellular PPIA activities in several different cell lines that included epithelial and monocytic cells.</p> <p>Results</p> <p>Our findings have revealed that extracellular PPIA activity is cell type-dependent and that PPIA signals via multiple cellular receptors beyond the single transmembrane receptor previously identified, Extracellular Matrix MetalloPRoteinase Inducer (EMMPRIN). Finally, while our studies provide important insight into the cell-specific responses, they also indicate that there are consistent responses such as nuclear factor kappa B (NFκB) signaling induced in all cell lines tested.</p> <p>Conclusions</p> <p>We conclude that although extracellular PPIA activates several common pathways, it also targets different receptors in different cell types, resulting in a complex, integrated signaling network that is cell type-specific.</p> Extracellular cyclophilin-APPIABSGEMMPRINCD147MMPCytokineInterleukinsPancreatic cancerLeukemia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bahmed Karim Henry Curtis Holliday Michael Redzic Jasmina Ciobanu Madalina Zhang Fengli Weekes Colin Sclafani Robert DeGregori James Eisenmesser Elan |
spellingShingle |
Bahmed Karim Henry Curtis Holliday Michael Redzic Jasmina Ciobanu Madalina Zhang Fengli Weekes Colin Sclafani Robert DeGregori James Eisenmesser Elan Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B Cancer Cell International Extracellular cyclophilin-A PPIA BSG EMMPRIN CD147 MMP Cytokine Interleukins Pancreatic cancer Leukemia |
author_facet |
Bahmed Karim Henry Curtis Holliday Michael Redzic Jasmina Ciobanu Madalina Zhang Fengli Weekes Colin Sclafani Robert DeGregori James Eisenmesser Elan |
author_sort |
Bahmed Karim |
title |
Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B |
title_short |
Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B |
title_full |
Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B |
title_fullStr |
Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B |
title_full_unstemmed |
Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B |
title_sort |
extracellular cyclophilin-a stimulates erk1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa b |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2012-07-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Although the peptidyl-prolyl isomerase, cyclophilin-A (peptidyl-prolyl isomerase, PPIA), has been studied for decades in the context of its intracellular functions, its extracellular roles as a major contributor to both inflammation and multiple cancers have more recently emerged. A wide range of activities have been ascribed to extracellular PPIA that include induction of cytokine and matrix metalloproteinase (MMP) secretion, which potentially underlie its roles in inflammation and tumorigenesis. However, there have been conflicting reports as to which particular signaling events are under extracellular PPIA regulation, which may be due to either cell-dependent responses and/or the use of commercial preparations recently shown to be highly impure.</p> <p>Methods</p> <p>We have produced and validated the purity of recombinant PPIA in order to subject it to a comparative analysis between different cell types. Specifically, we have used a combination of multiple methods such as luciferase reporter screens, translocation assays, phosphorylation assays, and nuclear magnetic resonance to compare extracellular PPIA activities in several different cell lines that included epithelial and monocytic cells.</p> <p>Results</p> <p>Our findings have revealed that extracellular PPIA activity is cell type-dependent and that PPIA signals via multiple cellular receptors beyond the single transmembrane receptor previously identified, Extracellular Matrix MetalloPRoteinase Inducer (EMMPRIN). Finally, while our studies provide important insight into the cell-specific responses, they also indicate that there are consistent responses such as nuclear factor kappa B (NFκB) signaling induced in all cell lines tested.</p> <p>Conclusions</p> <p>We conclude that although extracellular PPIA activates several common pathways, it also targets different receptors in different cell types, resulting in a complex, integrated signaling network that is cell type-specific.</p> |
topic |
Extracellular cyclophilin-A PPIA BSG EMMPRIN CD147 MMP Cytokine Interleukins Pancreatic cancer Leukemia |
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