The Invasion Protein InIB From Listeria Monocytogenes Activates PLC-gamma1 Downstream From PI 3-kinase

Cell Microbiol. 2000 Dec;2(6):465-76. doi: 10.1046/j.1462-5822.2000.00069.x.

Abstract

Entry of the bacterial pathogen Listeria monocytogenes into non-phagocytic mammalian cells is mainly mediated by the InlB protein. Here we show that in the human epithelial cell line HEp-2, the invasion protein InlB activates sequentially a p85beta-p110 class I(A) PI 3-kinase and the phospholipase C-gamma1 (PLC-gamma1) without detectable tyrosine phosphorylation of PLC-gamma1. Purified InlB stimulates association of PLC-gamma1 with one or more tyrosine-phosphorylated proteins, followed by a transient increase in intracellular inositol 1,4,5-trisphosphate (IP3) levels and a release of intracellular Ca2+ in a PI 3-kinase-dependent manner. Infection of HEp-2 cells with wild-type L. monocytogenes bacteria also induces association of PLC-gamma1 with phosphotyrosyl proteins. This interaction is undetectable upon infection with a deltainlB mutant revealing an InlB specific signal. Interestingly, pharmacological or genetic inactivation of PLC-gamma1 does not significantly affect InlB-mediated bacterial uptake, suggesting that InlB-mediated PLC-gamma1 activation and calcium mobilization are involved in post-internalization steps.

Publication types

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

MeSH terms

  • Bacterial Proteins
  • Calcium / metabolism
  • Enzyme Activation
  • Epithelial Cells / microbiology
  • Humans
  • Isoenzymes / metabolism*
  • Listeria monocytogenes / pathogenicity*
  • Listeria monocytogenes / physiology
  • Listeriosis / microbiology*
  • Membrane Proteins / metabolism
  • Membrane Proteins / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phospholipase C gamma
  • Phosphorylation
  • Tumor Cells, Cultured
  • Type C Phospholipases / metabolism*
  • Tyrosine / metabolism
  • Virulence

Substances

  • Bacterial Proteins
  • Isoenzymes
  • Membrane Proteins
  • inlB protein, Listeria monocytogenes
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • Calcium