2000
DOI: 10.1128/iai.68.10.6066-6068.2000
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Pseudomonas aeruginosa ExoT Is a Rho GTPase-Activating Protein

Abstract: Transient intracellular expression of ExoT in CHO cells stimulated cell rounding and actin reorganization. Biochemical studies showed that ExoT was a GTPase-activating protein for RhoA, Rac1, and Cdc42. Together, these data show that ExoT interferes with Rho signal transduction pathways, which regulate actin organization, exocytosis, cell cycle progression, and phagocytosis.

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Cited by 154 publications
(131 citation statements)
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“…Consistent with this notion, P. aeruginosa strains in which the ExoT gene is deleted exhibit reduced virulence and seem to be particularly defective in dissemination in mice (9)(10)(11)(12). ExoT possesses an N-terminal GTPase-activating protein (GAP) domain with activity toward Rho family GTPases (13,14) and is primarily responsible for the ExoT-mediated cell rounding, inhibition of cell migration, and antiinternalization activities (9,14). At its C terminus, ExoT contains an ADP-ribosyl transferase (ADPRT) domain, recently shown to target the Crk adaptor proteins and to interfere with their ability to interact with paxillin and p130Cas, resulting in inhibition of cell migration and cell rounding (15,16).…”
mentioning
confidence: 55%
“…Consistent with this notion, P. aeruginosa strains in which the ExoT gene is deleted exhibit reduced virulence and seem to be particularly defective in dissemination in mice (9)(10)(11)(12). ExoT possesses an N-terminal GTPase-activating protein (GAP) domain with activity toward Rho family GTPases (13,14) and is primarily responsible for the ExoT-mediated cell rounding, inhibition of cell migration, and antiinternalization activities (9,14). At its C terminus, ExoT contains an ADP-ribosyl transferase (ADPRT) domain, recently shown to target the Crk adaptor proteins and to interfere with their ability to interact with paxillin and p130Cas, resulting in inhibition of cell migration and cell rounding (15,16).…”
mentioning
confidence: 55%
“…ExoS and ExoT are highly related and have dual functions, acting as both a GTPase-activating protein (11)(12)(13)(14) and ADP-ribosyl transferase (15), and ExoY has been identified as an adenylate cyclase (16). Interestingly, the ADP-ribosyl transferase activities of ExoS and ExoT and the adenylate cyclase activity of ExoY are dependent on host cell factors, the 14-3-3 protein FAS for ExoS and ExoT (17), and unidentified factors for ExoY (16).…”
mentioning
confidence: 99%
“…The ADPRT activity of ExoT, however, targets the cellular Crk-I and Crk-II kinases rather than Ras (Sun & Barbieri, 2003). As a result, ExoT intoxication is associated with inhibition of bacterial internalization but not cytotoxicity (Cowell et al, 2000;Garrity-Ryan et al, 2000;Krall et al, 2000). ExoU possesses phospholipase A 2 and lysophospholipase activities (Phillips et al, 2003;Rabin & Hauser, 2005;Sato et al, 2003;Tamura et al, 2004) that lead to rapid lysis of mammalian cells (Coburn & Frank, 1999; Finck-Barbançon et al, 1997;Fleiszig et al, 1997;Hauser et al, 1998a;Vallis et al, 1999).…”
mentioning
confidence: 99%