PMID- 12139625
OWN - NLM
STAT- MEDLINE
DCOM- 20030110
LR  - 20211203
IS  - 0950-382X (Print)
IS  - 0950-382X (Linking)
VI  - 45
IP  - 3
DP  - 2002 Aug
TI  - YopH prevents monocyte chemoattractant protein 1 expression in macrophages and 
      T-cell proliferation through inactivation of the phosphatidylinositol 3-kinase 
      pathway.
PG  - 805-15
AB  - Phosphatidylinositol 3-kinase (PI 3-kinase) and its target protein kinase B (Akt) 
      are involved in various processes including internalization, chemotaxis and 
      proliferation. We analysed the activation of Akt in J774 macrophages infected 
      with virulent (pYV+) or avirulent (pYV-) Yersinia enterocolitica. During the 
      early stage of infection with pYV+ and pYV- bacteria, Akt and its targets, 
      glycogen synthase kinase 3 (GSK-3) and forkhead transcription factor (FKHRL1), 
      became phosphorylated. This phosphorylation induction was inhibited by wortmannin 
      and thus dependent on PI 3-kinase. When infection was carried out with pYV+ 
      bacteria but not with pYV- bacteria, Akt and its targets became dephosphorylated 
      at later time points. Using single knock-out mutants in bacterial effector genes, 
      we have determined that the tyrosine phosphatase YopH was responsible for the 
      inactivation of the PI 3-kinase cascade. In macrophages, this inactivation 
      correlated with the downregulation of mRNA coding for monocyte chemoattractant 
      protein 1 (MCP-1), suggesting that YopH inhibits recruitment of macrophages to 
      lymph nodes. We also analysed the effects of Y. enterocolitica infection on the 
      proliferation of T lymphocytes. Consistent with the observation that YopH 
      inactivated the Akt pathway, YopH inhibited PI 3-kinase-dependent secretion of 
      interleukin 2 and proliferation. These data reveal a new effect of YopH in 
      Yersinia pathogenesis.
FAU - Sauvonnet, Nathalie
AU  - Sauvonnet N
AD  - Microbial Pathogenesis Unit, Christian de Duve, Institute of Cellular Pathology 
      and Universite Catholique de Louvain, Brussels, Belgium.
FAU - Lambermont, Isabelle
AU  - Lambermont I
FAU - van der Bruggen, Pierre
AU  - van der Bruggen P
FAU - Cornelis, Guy R
AU  - Cornelis GR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mol Microbiol
JT  - Molecular microbiology
JID - 8712028
RN  - 0 (Androstadienes)
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (yopH protein, Yersinia)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Bacterial Outer Membrane Proteins/*pharmacology
MH  - Bacterial Proteins/*pharmacology
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Chemokine CCL2/*metabolism
MH  - Down-Regulation
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression/*drug effects
MH  - Macrophages/*drug effects/metabolism
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/*metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Protein Tyrosine Phosphatases/*pharmacology
MH  - Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-akt
MH  - RNA, Messenger/metabolism
MH  - T-Lymphocytes/cytology/*drug effects
MH  - Virulence
MH  - Wortmannin
MH  - Yersinia enterocolitica/*chemistry
EDAT- 2002/07/26 10:00
MHDA- 2003/01/11 04:00
CRDT- 2002/07/26 10:00
PHST- 2002/07/26 10:00 [pubmed]
PHST- 2003/01/11 04:00 [medline]
PHST- 2002/07/26 10:00 [entrez]
AID - 3053 [pii]
AID - 10.1046/j.1365-2958.2002.03053.x [doi]
PST - ppublish
SO  - Mol Microbiol. 2002 Aug;45(3):805-15. doi: 10.1046/j.1365-2958.2002.03053.x.