The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.Helicobacter pylori frequently colonizes the human stomach (1), and hosts infected by cagA-positive strains are at increased risk of gastric cancer and peptic ulceration (2-10). H. pylori injects the CagA protein into host gastric epithelial cells via a type IV secretion system (11-16). The injected CagA is tyrosine-phosphorylated by Src family protein-tyrosine kinases and binds SHP2 (Src homology 2 domain-containing Src homology tyrosine phosphatase) (17-21); the CagA-SHP2 complex has been detected in human gastric mucosa (22,23).The IL6/gp130/STAT3 (interleukin-6/glycoprotein 130/signal transducer and activation of transcription 3) pathway has been shown to play a role in the development of gastric cancer (24, 25). IL6 exerts its biological activities through the receptor subunit gp130 (26). At least two functional modules of gp130 have been characterized; one encompasses four membranedistal Tyr(P) binding sites for the Src homology 2 domain of the latent transcription factors, STAT1 and STAT3. The other comprises the membrane-proximal Tyr(P) 757 residue responsible for the engagement of cytoplasmic SHP2 (26, 27).IL6 induces recruitment and homodimerization of gp130, potentially leading to balanced signaling through both the JAK/ STAT and SHP2/Ras/ERK signaling pathways (28, 29). However, disrupting this balance in the gp130 "knock-in" mouse induced premalignant lesions, including atrophy, intestinal metaplasia, dysplasia, and ultimately gastric cancer (24). Similarly, when the IL6 cytokine family signaling pathway is disrupted, increased STAT3 signaling may favor development of gastric adenomas, whereas increased SHP2/ERK 2 signaling may lead to mucosal inflammation (25,30).That cellular factors that are up-regulated in response to H. pylori could modulate SHP2/ERK or JAK/STAT signaling pathways suggests that H. pylori persistence and its consequent pathologies could be influenced by gp130-mediated signal transduction through these pathways (30). In this study, we examined the role of CagA tyrosine phosphorylation status in the activation of the SHP2/ERK and...

Nontoxic dose of capsaicin inhibited H. pylori-induced IL-8 production by gastric epithelial cells through the modulation of IkappaB-, NF-kappaB-, and IL-8 pathways. We conclude that capsaicin can be proposed as a potential anti-inflammatory drug by inhibition of the production of IL-8 in H. pylori-infected gastric epithelium.

Abstract. This study aimed to investigate the effect of Helicobacter pylori (H. pylori) infection on the sonic Hedgehog (Shh) signaling in gastric cancer. Shh, Patched (Ptch), and transcription factor Gli1 were overexpressed in H. pyloriinfected gastric cancer cells. The oncoprotein, CagA positive H. pylori resulted in significantly higher Shh expression. Pretreatment with MG-132 or PDTC significantly lowered Shh expression. Significant overexpression of Shh and Gli1 were noted in H. pylori-infected compared to non-infected gastric cancer tissues. Conclusively, H. pylori activated the Shh signaling pathway in CagA-dependent manner partly through the NF-κB pathway in gastric cancer cells.

MapReduce is a programing model used for parallelly processing a large amount of data. To analyze a large amount data, the data cube is widely used, which is an operator that computes group-bys for all possible combinations of given dimension attributes. When the number of dimension attributes is n, the data cube computes 2 n group-bys. In this paper, we propose an efficient method for computing data cubes using MapReduce. The proposed method partitions 2 n group-bys into n C⌈n/2⌉ batches, and computes those batches in stages using ⎡n/2⌉ MapReduce jobs. Compared to the existing methods, the proposed method significantly reduces the amount of intermediate data generated by mappers, so that the cost of sorting and transferring those intermediate data is reduced significantly. Consequently, the total processing time for computing a data cube is reduced. Through experiments, we show the efficiency of the proposed method over the existing methods.