PMID- 10973983
OWN - NLM
STAT- MEDLINE
DCOM- 20010108
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 47
DP  - 2000 Nov 24
TI  - Phosphatidylinositol 3-kinase activation and interaction with focal adhesion 
      kinase in Escherichia coli K1 invasion of human brain microvascular endothelial 
      cells.
PG  - 36769-74
AB  - Invasion of brain microvascular endothelial cells (BMEC) is a prerequisite for 
      successful crossing of the blood-brain barrier by Escherichia coli K1. We have 
      previously demonstrated the requirement of cytoskeletal rearrangements and 
      activation of focal adhesion kinase (FAK) in E. coli K1 invasion of human BMEC 
      (HBMEC). The current study investigated the role of phosphatidylinositol 3-kinase 
      (PI3K) activation and PI3K interaction with FAK in E. coli invasion of HBMEC. 
      PI3K inhibitor LY294002 blocked E. coli K1 invasion of HBMEC in a dose-dependent 
      manner, whereas an inactive analogue LY303511 had no such effect. In HBMEC, E. 
      coli K1 increased phosphorylation of Akt, a downstream effector of PI3K, which 
      was completely blocked by LY294002. In contrast, non-invasive E. coli failed to 
      activate PI3K. Overexpression of PI3K mutants Deltap85 and catalytically inactive 
      p110 in HBMEC significantly inhibited both PI3K/Akt activation and E. coli K1 
      invasion of HBMEC. Stimulation of HBMEC with E. coli K1 increased PI3K 
      association with FAK. Furthermore, PI3K/Akt activation was blocked in 
      HBMEC-overexpressing FAK dominant-negative mutants (FRNK and Phe397FAK). These 
      results demonstrated the involvement of PI3K signaling in E. coli K1 invasion of 
      HBMEC and identified a novel role for PI3K interaction with FAK in the 
      pathogenesis of E. coli meningitis.
FAU - Reddy, M A
AU  - Reddy MA
AD  - Division of Infectious Diseases, Childrens Hospital Los Angeles, CA, USA.
FAU - Prasadarao, N V
AU  - Prasadarao NV
FAU - Wass, C A
AU  - Wass CA
FAU - Kim, K S
AU  - Kim KS
LA  - eng
GR  - AI-47225/AI/NIAID NIH HHS/United States
GR  - HL-61951/HL/NHLBI NIH HHS/United States
GR  - R01-NS-26310/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (PTK2 protein, human)
SB  - IM
MH  - Blood-Brain Barrier
MH  - Brain/*microbiology
MH  - Cells, Cultured
MH  - *Cerebrovascular Circulation
MH  - Chromones/pharmacology
MH  - Endothelium, Vascular/*enzymology/*microbiology
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Escherichia coli/enzymology/*pathogenicity
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Humans
MH  - Microcirculation
MH  - Morpholines/pharmacology
MH  - Mutagenesis, Site-Directed
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Signal Transduction
MH  - Structure-Activity Relationship
EDAT- 2000/09/07 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/07 11:00
PHST- 2000/09/07 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/07 11:00 [entrez]
AID - S0021-9258(20)88581-0 [pii]
AID - 10.1074/jbc.M007382200 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Nov 24;275(47):36769-74. doi: 10.1074/jbc.M007382200.