PMID- 12052963
OWN - NLM
STAT- MEDLINE
DCOM- 20020624
LR  - 20091119
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Linking)
VI  - 296
IP  - 5574
DP  - 2002 Jun 7
TI  - Activation of endothelial cell protease activated receptor 1 by the protein C 
      pathway.
PG  - 1880-2
AB  - The coagulant and inflammatory exacerbation in sepsis is counterbalanced by the 
      protective protein C (PC) pathway. Activated PC (APC) was shown to use the 
      endothelial cell PC receptor (EPCR) as a coreceptor for cleavage of protease 
      activated receptor 1 (PAR1) on endothelial cells. Gene profiling demonstrated 
      that PAR1 signaling could account for all APC-induced protective genes, including 
      the immunomodulatory monocyte chemoattractant protein-1 (MCP-1), which was 
      selectively induced by activation of PAR1, but not PAR2. Thus, the prototypical 
      thrombin receptor is the target for EPCR-dependent APC signaling, suggesting a 
      role for this receptor cascade in protection from sepsis.
FAU - Riewald, Matthias
AU  - Riewald M
AD  - Department of Immunology, C204, The Scripps Research Institute, 10550 North 
      Torrey Pines Road, La Jolla, CA 92037, USA.
FAU - Petrovan, Ramona J
AU  - Petrovan RJ
FAU - Donner, Aaron
AU  - Donner A
FAU - Mueller, Barbara M
AU  - Mueller BM
FAU - Ruf, Wolfram
AU  - Ruf W
LA  - eng
GR  - P01-HL16411/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NR4A1 protein, human)
RN  - 0 (Nr4a1 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (Protein C)
RN  - 0 (Receptor, PAR-1)
RN  - 0 (Receptor, PAR-2)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Receptors, Thrombin)
RN  - 0 (Transcription Factors)
RN  - 0 (activated protein C receptor)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Animals
MH  - *Blood Coagulation Factors
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - DNA-Binding Proteins/genetics
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Enzyme Activation
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Humans
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphorylation
MH  - Protein C/*metabolism
MH  - Receptor, PAR-1
MH  - Receptor, PAR-2
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Cytoplasmic and Nuclear
MH  - Receptors, Steroid
MH  - Receptors, Thrombin/agonists/*metabolism
MH  - Signal Transduction
MH  - Thrombin/metabolism
MH  - Transcription Factors/genetics
EDAT- 2002/06/08 10:00
MHDA- 2002/06/25 10:01
CRDT- 2002/06/08 10:00
PHST- 2002/06/08 10:00 [pubmed]
PHST- 2002/06/25 10:01 [medline]
PHST- 2002/06/08 10:00 [entrez]
AID - 296/5574/1880 [pii]
AID - 10.1126/science.1071699 [doi]
PST - ppublish
SO  - Science. 2002 Jun 7;296(5574):1880-2. doi: 10.1126/science.1071699.