S. Typhimurium Encodes an Activator of Rho GTPases That Induces Membrane Ruffling and Nuclear Responses in Host Cells

Cell. 1998 May 29;93(5):815-26. doi: 10.1016/s0092-8674(00)81442-7.

Abstract

S. typhimurium stimulates signaling pathways leading to membrane ruffling, actin cytoskeleton rearrangements, and nuclear responses. The stimulation requires a protein secretion system (type III) that translocates bacterial proteins into the host cell. We show that SopE, a substrate of this secretion system, stimulates cytoskeletal reorganization and JNK activation in a CDC42- and Rac-1-dependent manner. A lambda gt11 cDNA library screen for proteins that interact with SopE identified Rac-1 and CDC42. Furthermore, purified SopE was shown to stimulate GDP/GTP nucleotide exchange in several Rho GTPases in vitro, including Rac-1 and CDC42. These findings establish a paradigm for microbial stimulation of cellular responses in which the pathogen induces signaling events by directly engaging the signaling machinery within the host cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Membrane
  • Cell Nucleus
  • Cytoskeleton
  • Enzyme Activation
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases*
  • Proteins / metabolism
  • Salmonella typhimurium / pathogenicity*
  • Signal Transduction
  • cdc42 GTP-Binding Protein

Substances

  • Bacterial Proteins
  • Cell Cycle Proteins
  • GTPase-Activating Proteins
  • Proteins
  • SopE protein, Salmonella
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein