Aktories K, Schmidt G, Just I
Institut für Pharmakologie und Toxikologie der Universität Freiburg, Germany.
Biol Chem. 2000 May-Jun;381(5-6):421-6. doi: 10.1515/BC.2000.054.
Several bacterial toxins target Rho GTPases, which constitute molecular switches in several signaling processes and master regulators of the actin cytoskeleton. The biological activities of Rho GTPases are blocked by C3-like transferases, which ADP-ribosylate Rho at Asn41, but not Rac or Cdc42. Large clostridial cytotoxins (e. g., Clostridium difficile toxin A and B) glucosylate Rho GTPases at Thr37 (Rho) or Thr35 (Rac/Cdc42), thereby inhibiting Rho functions by preventing effector coupling. The 'injected' toxins ExoS, YopE and SptP from Pseudomonas aeruginosa, Yersinia and Salmonella ssp., respectively, which are transferred into the eukaryotic target cells by the type-III secretion system, inhibit Rho functions by acting as Rho GAP proteins. Rho GTPases are activated by the cytotoxic necrotizing factors CNF1 and CNF2 from Escherichia coli and by the dermonecrotizing toxin DNT from B. bronchiseptica. These toxins deamidate/transglutaminate Gln63 of Rho to block the intrinsic and GAP-stimulated GTP hydrolysis, thereby constitutively activating the GTPases. Rho GTPases are also activated by SopE, a type-III system injected protein from Salmonella ssp., that acts as a GEF protein.
几种细菌毒素作用于Rho GTP酶，Rho GTP酶在多个信号传导过程中构成分子开关，是肌动蛋白细胞骨架的主要调节因子。Rho GTP酶的生物活性被C3样转移酶阻断，该酶在Asn41位点对Rho进行ADP核糖基化，但不对Rac或Cdc42进行修饰。大型梭菌细胞毒素（如艰难梭菌毒素A和B）在Thr37（Rho）或Thr35（Rac/Cdc42）位点对Rho GTP酶进行糖基化，从而通过阻止效应器偶联来抑制Rho功能。分别来自铜绿假单胞菌、耶尔森菌和沙门氏菌属的“注入型”毒素ExoS、YopE和SptP，通过III型分泌系统转移到真核靶细胞中，作为Rho GAP蛋白发挥作用来抑制Rho功能。Rho GTP酶被大肠杆菌的细胞毒性坏死因子CNF1和CNF2以及支气管败血波氏杆菌的皮肤坏死毒素DNT激活。这些毒素使Rho的Gln63脱酰胺/转谷氨酰胺化，以阻断内在的和GAP刺激的GTP水解，从而组成性激活GTP酶。Rho GTP酶也被SopE激活，SopE是一种来自沙门氏菌属的III型系统注入蛋白，作为一种GEF蛋白发挥作用。
