Hierarchical cleavage of focal adhesion kinase by caspases alters signal transduction during apoptosis of intestinal epithelial cells

Grossmann, Johannes; Artinger, Monika; Grasso, Adam W.; Kung, Hsing Jien; Schölmerich, Jürgen; Fiocchi, Claudio; Levine, Alan D.

doi:10.1053/gast.2001.20879

Cited by 56 publications

(33 citation statements)

References 47 publications

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“…This suggests that, at higher concentrations, NO may interact with other, as yet unidentified, target molecules that are responsible for a further decrease in ability of human MC to adhere to FN. These additional target molecules could include other cysteine proteases, such as caspases that are known to play a role in cleavage of FAK (48,49). However, we have observed that Z-VAD-FMK, an inhibitor of caspases 1, 3, 4, and 7, does not alter MC adhesion to FN (our unpublished observations).…”

Section: Discussionmentioning

confidence: 81%

Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion

Forsythe

Befus

2003

The Journal of Immunology

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Nitric oxide is an important messenger that regulates mast cell activity by modifications to gene expression and intracellular pathways associated with exocytosis and adhesion. Integrin interactions with extracellular matrix components modulate an array of cell activities, including mediator production and secretion. To investigate the molecular mechanisms underlying NO regulation of mast cell function, we studied its effects on adhesion of a human mast cell line (HMC-1) to fibronectin (FN). The NO donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine strongly down-regulated the adhesion of HMC-1 to FN. Inhibitors of soluble guanylate cyclase and protein kinase G did not alter the response of cells to NO. A peroxynitrite scavenger did not affect modulation of adhesion by NO, nor could the effect of NO be mimicked by the peroxynitrite-producing compound 3-morpholinosydnonimine. NO donors inhibited the cysteine protease, calpain, while calpain inhibitors mimicked the effect of NO and led to a decrease in the ability of HMC-1 cells to adhere to FN. Thus, NO is an effective down-regulator of human mast cell adhesion. The mechanism for this action does not involve peroxynitrite or activation of soluble guanylate cyclase. Instead, a portion of NO-induced down-regulation of adhesion may be attributed to inhibition of the cysteine protease, calpain, an enzyme that has been associated with control of integrin activation in other cell types. The inhibition of calpain is most likely mediated via nitrosylation of its active site thiol group. Calpain may represent a novel therapeutic target for the regulation of mast cell activity in inflammatory disorders.

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Section: Discussionmentioning

confidence: 81%

Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion

Forsythe

Befus

2003

The Journal of Immunology

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“…Moreover, Fak1 has recently been shown to be a critical protein in survival signalling, since it blocks apoptosis induced by several stimuli [49]. Fak1 expression decrease following proteolytic cleavage in various cell types has been associated with various cell dysfunctions including c-Myc-induced apoptosis of chicken embryo fibroblasts (CEF) [49], growth factor deprivation-induced apoptosis of human umbilical vein endothelial cells [50], and detachment-induced cell death (anoikis) of intestinal epithelial cells [51]. In a recent study, different epithelial cell lines treated with thimerosal displayed increased levels of hydrogen peroxide resulting in caspase activation, Fak1 cleavage and apoptosis [52].…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of cells exposed to prefibrillar aggregates of HypF-N

Magherini

Pieri

Guidi

et al. 2009

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Several human diseases are associated with the deposition of stable ordered protein aggregates known as amyloid fibrils. In addition, a large wealth of data shows that proteins not involved in amyloidoses, are able to form, in vitro, amyloid-like prefibrillar and fibrillar assemblies indistinguishable from those grown from proteins associated with disease. Previous studies showed that early prefibrillar aggregates of the N-terminal domain of the prokaryotic hydrogenase maturation factor HypF (HypF-N) are cytotoxic, inducing early mitochondria membrane depolarization, activation of caspase 9 and eventually cell death. To gain knowledge on the molecular basis of HypF-N aggregate cytotoxicity, we performed a differential proteomic analysis of NIH-3T3 cells exposed to HypF-N prefibrillar aggregates in comparison with control cells. Two-dimensional gel electrophoresis followed by protein identification by MALDI-TOF MS, allowed us to identify 21 proteins differentially expressed. The changes of the expression level of proteins involved in stress response (Hsp60 and 78 kDa glucose-regulated protein) and in signal transduction (Focal adhesion kinase1) appear particularly interesting as possible determinants of the cell fate. The levels of some of the differently expressed proteins were modified also in similar studies carried out on cells exposed to Aβ or α-synuclein aggregates, supporting the existence of shared features of amyloid cytotoxicity.

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“…Thus, ER stress resulting from SubAB-induced BiP cleavage precedes FAK degradation. Proteolytic cleavage of FAK has been reported in various cell types during apoptosis (13,25,41,46). FAK cleavage was shown to be induced by activation of calpain-like intracellular proteases (8) or caspases (23,41,42,62,71) in fibroblasts transformed by the v-src or myc oncogene (13,20) or by a proteasome-dependent pathway (36,53).…”

Section: Effect Of ␤1 Integrin Knockdown On Thapsigargin-induced Caspmentioning

confidence: 99%

Identification of Subtilase Cytotoxin (SubAB) Receptors Whose Signaling, in Association with SubAB-Induced BiP Cleavage, Is Responsible for Apoptosis in HeLa Cells

et al. 2011

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Subtilase cytotoxin (SubAB), which is produced by certain strains of Shiga-toxigenic Escherichia coli (STEC), causes the 78-kDa glucose-regulated protein (GRP78/BiP) cleavage, followed by induction of endoplasmic reticulum (ER) stress, leading to caspase-dependent apoptosis via mitochondrial membrane damage by Bax/Bak activation. The purpose of the present study was to identify SubAB receptors responsible for HeLa cell death. Four proteins, NG2, ␣2␤1 integrin (ITG), L1 cell adhesion molecule (L1CAM), and hepatocyte growth factor receptor (Met), were identified to be SubAB-binding proteins by immunoprecipitation and purification, followed by liquid chromatography-tandem mass spectrometry analysis. SubAB-induced Bax conformational change, Bax/Bak complex formation, caspase activation, and cell death were decreased in ␤1 ITG, NG2, and L1CAM small interfering RNAtransfected cells, but unexpectedly, BiP cleavage was still observed. Pretreatment of cells with a function-blocking ␤1 ITG antibody (monoclonal antibody [MAb] P5D2) enhanced SubAB-induced caspase activation; MAb P5D2 alone had no effect on caspase activation. Furthermore, we found that SubAB induced focal adhesion kinase fragmentation, which was mediated by a proteasome-dependent pathway, and caspase activation was suppressed in the presence of proteasome inhibitor. Thus, ␤1 ITG serves as a SubAB-binding protein and may interact with SubAB-signaling pathways, leading to cell death. Our results raise the possibility that although BiP cleavage is necessary for SubAB-induced apoptotic cell death, signaling pathways associated with functional SubAB receptors may be required for activation of SubAB-dependent apoptotic pathways.

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Hierarchical cleavage of focal adhesion kinase by caspases alters signal transduction during apoptosis of intestinal epithelial cells

Cited by 56 publications

References 47 publications

Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion

Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion

Proteomic analysis of cells exposed to prefibrillar aggregates of HypF-N

Identification of Subtilase Cytotoxin (SubAB) Receptors Whose Signaling, in Association with SubAB-Induced BiP Cleavage, Is Responsible for Apoptosis in HeLa Cells

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