2006
DOI: 10.1016/j.cell.2005.10.031
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Identification of a Bacterial Type III Effector Family with G Protein Mimicry Functions

Abstract: Many bacterial pathogens use the type III secretion system to inject "effector" proteins into host cells. Here, we report the identification of a 24 member effector protein family found in pathogens including Salmonella, Shigella, and enteropathogenic E. coli. Members of this family subvert host cell function by mimicking the signaling properties of Ras-like GTPases. The effector IpgB2 stimulates cellular responses analogous to GTP-active RhoA, whereas IpgB1 and Map function as the active forms of Rac1 and Cdc… Show more

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Cited by 250 publications
(400 citation statements)
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“…This activity could possibly be the regulation of another molecular motor such as dynein because inhibition of dynein activity has been shown to stabilize the sifA Ϫ SCV to the same extent as does inhibition of kinesin activity (18), and this retrograde molecular motor is recruited onto the SCV by binding to a rab7͞RILP complex under certain circumstances (24,25). SifA contains a pentapeptide motif that has the potential to mimic small GTPases in their active GTP-bound form (26) and thus could potentially modulate the rab7͞RILP͞dynein cascade (27). Finally, a double sifA Ϫ ͞sseJ Ϫ mutant does not lose its vacuole (28), suggesting that SifA and SseJ exert antagonist activities.…”
Section: Discussionmentioning
confidence: 99%
“…This activity could possibly be the regulation of another molecular motor such as dynein because inhibition of dynein activity has been shown to stabilize the sifA Ϫ SCV to the same extent as does inhibition of kinesin activity (18), and this retrograde molecular motor is recruited onto the SCV by binding to a rab7͞RILP complex under certain circumstances (24,25). SifA contains a pentapeptide motif that has the potential to mimic small GTPases in their active GTP-bound form (26) and thus could potentially modulate the rab7͞RILP͞dynein cascade (27). Finally, a double sifA Ϫ ͞sseJ Ϫ mutant does not lose its vacuole (28), suggesting that SifA and SseJ exert antagonist activities.…”
Section: Discussionmentioning
confidence: 99%
“…Most AvrE family members contain a putative endoplasmic reticulum membrane retention signal (ERMRS) and one or two WxxxE motifs (Ham et al, 2009). The WxxxE motifs were first discovered in T3Es of animal pathogens (Alto et al, 2006). Derivatives of WtsE with either the putative ERMRS or both WxxxE motifs mutated (DFEMK and w12 mutants, respectively) failed to elicit disease symptoms in maize or to suppress defense responses in Arabidopsis (Ham et al, 2009).…”
mentioning
confidence: 99%
“…IpgB1 belongs to the so-called "WXXXE" type-III effector family, formerly proposed to act as mimics of RhoGTPases, but for which there are structural and enzymatic activity evidence that this family rather corresponds to GEFs (guanosine exchange factor) for small GTPases ( Fig. 1) (Alto et al 2006;Bulgin et al 2010;Orchard and Alto 2012). The picture is blurred by evidence that the same WXXXE effectors recruit GEFs for the GTPase.…”
Section: The Ipab and Ipac Translocon Components And Tyrosine Kinase mentioning
confidence: 92%
“…IpgB2, first described as a Rho mimic, may also activate Rho through its GEF activity, or through the activation of GEF-H1 (Alto et al 2006;Fukazawa et al 2008). A role for IpgB2 in Shigella invasion is observed in polarized but not in nonpolarized cells and only in combination with IpgB1 (Hachani et al 2008).…”
Section: The Ipab and Ipac Translocon Components And Tyrosine Kinase mentioning
confidence: 99%
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