Related Experiment Video

Updated: Jun 11, 2026

A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication
09:52

A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication

Published on: September 20, 2016

Activation of endothelial cell protease activated receptor 1 by the protein C pathway

Matthias Riewald1, Ramona J Petrovan, Aaron Donner

  • 1Department of Immunology, C204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Science (New York, N.Y.)
|June 8, 2002
PubMed

Insights

The protein C (PC) pathway protects against sepsis. Activated PC (APC) uses EPCR to signal through PAR1, inducing protective genes like MCP-1, crucial for sepsis defense.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Immunology

Background:

  • Sepsis involves harmful coagulation and inflammation.
  • The protein C (PC) pathway offers protection against sepsis.
  • Activated protein C (APC) interacts with endothelial cells.

Purpose of the Study:

  • To investigate the mechanism of APC's protective effects in sepsis.
  • To identify the specific receptor and signaling pathway involved in APC's protective actions.
  • To determine if PAR1 signaling mediates APC-induced protective gene expression.

Main Methods:

  • Gene profiling to analyze gene expression changes induced by APC.
  • Investigating the role of endothelial cell PC receptor (EPCR) as a coreceptor.
  • Examining the cleavage of protease-activated receptor 1 (PAR1) by APC.
  • Comparing signaling through PAR1 versus PAR2.

Main Results:

  • APC utilizes EPCR as a coreceptor for PAR1 cleavage on endothelial cells.
  • PAR1 signaling fully explains the induction of all APC-protective genes.
  • Monocyte chemoattractant protein-1 (MCP-1), an immunomodulatory gene, was selectively induced by PAR1 activation.
  • PAR2 activation did not induce MCP-1.

Conclusions:

  • The prototypical thrombin receptor, PAR1, is the target for EPCR-dependent APC signaling.
  • This receptor cascade plays a significant role in protecting against sepsis.
  • Targeting the EPCR-PAR1 pathway could offer therapeutic strategies for sepsis.

More Related Videos

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins11:25

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins

Published on: October 4, 2017

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Related Concept Videos

Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...