Say NO to insulin

H. pylori mobilizes cells elicobacter pylori infects the gastric track of more than half of the human population and is associated with an increased occurrence of invasive gastric cancers. On page 249, Churin et al. explain how this widespread bug turns tumors metastatic by corrupting a growth factor receptor. H H. pylori infection mobilizes gastric epithelial cells (right) by activating c-Met. H. pylori mobilizes infected epithelial cells on its course to pathogenicity. The authors now show that mobilization results from activation of the hepatocyte growth factor (HGF) receptor c-Met. During development and differentiation, HGF-induced activation of c-Met initiates cell migration events. Inhibition of c-Met expression by siRNA blocks H. pylori –induced motility. H. pylori corrupts c-Met signaling, however, by injecting host cells with the protein CagA. Binding of CagA to c-Met resulted in modulation of receptor activity and recruitment of PLC ␥ , a mediator of cell polarity necessary for motility. CagA–PLC ␥ interactions mobilized infected cells through an ERK-dependent MAP kinase pathway, as inhibitors of MAP kinases or PLC ␥ blocked motility. Unlike the gastric tumor cell line, a polarized canine kidney cell line does scatter in response to HGF. H pylori also induced c-Met–mediated motility in these cells, but did so through a PI3K-dependent pathway rather than through PLC ␥ , indicating that the bug uses alternative routes to motility depending on the cell type. The authors hope to look at animal models next to determine whether inappropriate activation of c-Met and the resulting mobilization of gastric cells is responsible for increased incidences of metastatic cancers in H. pylori infections. ᭿ Say NO to insulin nsulin stimulates its own secretion from pancreatic ␤ cells through rapid nitrosylation of glucokinase (GK), according to results by Rizzo and Piston on page 243. When glucose levels are low, an inhibited form of GK associates with insulin-containing granules in pancreatic ␤ cells. Rizzo and Piston have determined that this localization is mediated through interaction with neuronal nitric oxide synthase (nNOS). Insulin treatment disrupted this association through nitrosylation of a GK cysteine residue. Activation of nNOS and the resulting nitro-sylation of GK may be mediated through a rise in intracellular calcium, a known response of ␤ cells to insulin treatment. Release of the enzyme into the cytoplasm and the accompanying conform-ational change—both of which required NO production— activated GK. GK induces secretion of the granules, thus promoting local increases in insulin levels. A …