Exoenzyme S Shows Selective ADP-ribosylation and GTPase-activating Protein (GAP) Activities Towards Small GTPases in Vivo

Biochem J. 2002 Nov 1;367(Pt 3):617-28. doi: 10.1042/BJ20020714.

Abstract

Intracellular targeting of the Pseudomonas aeruginosa toxins exoenzyme S (ExoS) and exoenzyme T (ExoT) initially results in disruption of the actin microfilament structure of eukaryotic cells. ExoS and ExoT are bifunctional cytotoxins, with N-terminal GTPase-activating protein (GAP) and C-terminal ADP-ribosyltransferase activities. We show that ExoS can modify multiple GTPases of the Ras superfamily in vivo. In contrast, ExoT shows no ADP-ribosylation activity towards any of the GTPases tested in vivo. We further examined ExoS targets in vivo and observed that ExoS modulates the activity of several of these small GTP-binding proteins, such as Ras, Rap1, Rap2, Ral, Rac1, RhoA and Cdc42. We suggest that ExoS is the major ADP-ribosyltransferase protein modulating small GTPase function encoded by P. aeruginosa. Furthermore, we show that the GAP activity of ExoS abrogates the activation of RhoA, Cdc42 and Rap1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / metabolism*
  • Adenosine Diphosphate Ribose / metabolism*
  • Bacterial Toxins / metabolism*
  • GTP Phosphohydrolases / metabolism*
  • GTPase-Activating Proteins / metabolism*
  • HeLa Cells
  • Humans

Substances

  • Bacterial Toxins
  • GTPase-Activating Proteins
  • Adenosine Diphosphate Ribose
  • ADP Ribose Transferases
  • exoenzyme S
  • GTP Phosphohydrolases