Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here we describe a Rho-mediated apoptosis suppression pathway driven by Bcl-2 expression in the interleukin (IL)-4- or IL-2-dependent murine T cell line TS1 alpha beta. IL-2, but not IL-4, induces Bcl-2 expression through RhoA activation which is inhibited by the specific Rho family inhibitor, Clostridium difficile Toxin B, as well as by a dominant negative RhoA mutant. Using transient transfections of RhoA mutants tagged with the vesicular stomatitis virus glycoprotein, we show that a constitutively active RhoA mutant induces Bcl-2 expression and prevents apoptosis upon IL-4 withdrawal. Finally, we have identified the signaling pathway involved together with RhoA in Bcl-2 induction and show compelling evidence for the implication of phosphatidylinositol 3 kinase and protein kinase C.
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PMID:Rho prevents apoptosis through Bcl-2 expression: implications for interleukin-2 receptor signal transduction. 939 1

The cystic fibrosis transmembrane conductance regulator (CFTR)-interacting protein, CFTR-associated ligand (CAL) down-regulates total and cell surface CFTR by targeting CFTR for degradation in the lysosome. Here, we report that a Rho family small GTPase TC10 interacts with CAL. This interaction specifically up-regulates CFTR protein expression. Co-expression of the constitutively active form, TC10Q75L, increases total and cell surface CFTR in a dose-dependent fashion. Moreover, co-expression of the dominant-negative mutant TC10T31N causes a dose-dependent reduction in mature CFTR. The effect of TC10 is independent of the level of CFTR expression, because a similar effect was observed in a stable cell line that expresses one-tenth of CFTR. Co-expression of TC10Q75L did not have a similar effect on the expression of plasma membrane proteins such as Frizzled-3 and Pr-cadherin or cytosolic proteins such as tubulin and green fluorescent protein. TC10Q75L also did not have a similar effect on the vesicular stomatitis virus glycoprotein. Co-expression of constitutively active and dominant-negative forms of Cdc42 or RhoA did not affect CFTR expression in a manner similar to TC10, indicating that the effect of TC10 is unique within the Rho family. Metabolic pulse-chase experiments show that TC10 did not affect CFTR maturation, suggesting that it exerts its effects on the mature CFTR. Importantly, TC10Q75L reverses CAL-mediated CFTR degradation, suggesting that TC10Q75L inhibits CAL-mediated degradation of CFTR. TC10Q75L does not operate by reducing CAL protein expression or its ability to form dimers or interact with CFTR. Interestingly, the expression of TC10Q75L causes a dramatic redistribution of CAL from the juxtanuclear region to the plasma membrane where the two molecules overlap. These data suggest that TC10 regulates both total and plasma membrane CFTR expression by interacting with CAL. The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane, away from CAL-mediated degradation of CFTR in the lysosome.
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PMID:Regulation of cystic fibrosis transmembrane regulator trafficking and protein expression by a Rho family small GTPase TC10. 1554 64

The pathogen Salmonella Typhimurium is a common cause of diarrhea and invades the gut tissue by injecting a cocktail of virulence factors into epithelial cells, triggering actin rearrangements, membrane ruffling and pathogen entry. One of these factors is SopE, a G-nucleotide exchange factor for the host cellular Rho GTPases Rac1 and Cdc42. How SopE mediates cellular invasion is incompletely understood. Using genome-scale RNAi screening we identified 72 known and novel host cell proteins affecting SopE-mediated entry. Follow-up assays assigned these 'hits' to particular steps of the invasion process; i.e., binding, effector injection, membrane ruffling, membrane closure and maturation of the Salmonella-containing vacuole. Depletion of the COPI complex revealed a unique effect on virulence factor injection and membrane ruffling. Both effects are attributable to mislocalization of cholesterol, sphingolipids, Rac1 and Cdc42 away from the plasma membrane into a large intracellular compartment. Equivalent results were obtained with the vesicular stomatitis virus. Therefore, COPI-facilitated maintenance of lipids may represent a novel, unifying mechanism essential for a wide range of pathogens, offering opportunities for designing new drugs.
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PMID:RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42. 2140 11