Murli S, Watson R O, Galán J E
Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, New Haven, CT 06536, USA.
Cell Microbiol. 2001 Dec;3(12):795-810. doi: 10.1046/j.1462-5822.2001.00158.x.
Salmonella has evolved an intimate functional interface with its host. Central to this interface is a battery of bacterial proteins delivered into host cells via a specialized organelle termed the type III secretion system. A subset of these bacterial proteins stimulates cellular responses by activating the Rho family GTPases Cdc42 and Rac. Stimulation of these responses leads to actin cytoskeleton reorganization and the activation of cellular transcription factors that result in bacterial uptake and proinflammatory cytokine production. Remarkably, the cellular responses stimulated by Salmonella are quickly reversed by another bacterial protein, SptP, which exerts its function as a GTPase-activating protein (GAP) for Cdc42 and Rac. In addition to its GAP activity located within its amino-terminus, the carboxy-terminal domain of SptP possesses potent tyrosine phosphatase activity. We show here that the tyrosine phosphatase activity of SptP is involved in reversing the MAP kinase activation that results from Salmonella infection. We also demonstrate an important role for tyrosine kinases, including ACK, in the cellular responses induced by Salmonella. We also found that a potential target for the tyrosine phosphatase activity of SptP is the intermediate filament protein vimentin, which is recruited to the membrane ruffles stimulated by Salmonella.
沙门氏菌已经与其宿主进化出一种紧密的功能界面。这种界面的核心是一系列通过一种称为III型分泌系统的特殊细胞器递送到宿主细胞中的细菌蛋白。这些细菌蛋白的一个子集通过激活Rho家族GTP酶Cdc42和Rac来刺激细胞反应。这些反应的刺激导致肌动蛋白细胞骨架重组以及细胞转录因子的激活，从而导致细菌摄取和促炎细胞因子的产生。值得注意的是，沙门氏菌刺激的细胞反应会被另一种细菌蛋白SptP迅速逆转，SptP作为Cdc42和Rac的GTP酶激活蛋白（GAP）发挥其功能。除了其位于氨基末端的GAP活性外，SptP的羧基末端结构域还具有强大的酪氨酸磷酸酶活性。我们在此表明，SptP的酪氨酸磷酸酶活性参与逆转由沙门氏菌感染导致的MAP激酶激活。我们还证明了酪氨酸激酶，包括ACK，在沙门氏菌诱导的细胞反应中的重要作用。我们还发现，SptP酪氨酸磷酸酶活性的一个潜在靶点是中间丝蛋白波形蛋白，它被募集到由沙门氏菌刺激的膜皱褶处。
