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Literature summary for 3.4.21.69 extracted from

  • Minhas, N.; Xue, M.; Jackson, C.J.
    Activated protein C binds directly to Tie2 possible beneficial effects on endothelial barrier function (2017), Cell. Mol. Life Sci., 74, 1895-1906 .
    View publication on PubMed
Search for more literature for 3.4.21.69

Activating Compound

Activating Compound Comment Organism Structure
vitamin K dependent on Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ decreases the binding affinity of APC and Tie2 at 1 mM and 1-12 h Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
protease-activated receptor 1 + H2O Homo sapiens PAR1, cleavage at Arg46 ?
-
 ?
Tie2 + H2O Homo sapiens activated protein C binds directly to and activates Tie2. Tie2 is a transmembrane endothelial tyrosine kinase receptor that not only regulates vessel maturation and remodeling angiogenesis, but also controls endothelial inflammation and permeability ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P04070
-
-

Source Tissue

Source Tissue Comment Organism Textmining
endothelial cell
-
 Homo sapiens
-
umbilical vein endothelial cell HUVEC Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
protease-activated receptor 1 + H2O PAR1, cleavage at Arg46 Homo sapiens ?
-
 ?
Tie2 + H2O activation Homo sapiens ?
-
 ?
Tie2 + H2O activated protein C binds directly to and activates Tie2. Tie2 is a transmembrane endothelial tyrosine kinase receptor that not only regulates vessel maturation and remodeling angiogenesis, but also controls endothelial inflammation and permeability Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
? x * 56000, recombinant enzyme, SDS-PAGE Homo sapiens

Synonyms

Synonyms Comment Organism
Activated protein C
-
 Homo sapiens
APC
-
 Homo sapiens

General Information

General Information Comment Organism
malfunction blocking Tie2 restricts endothelial barrier integrity. On blocking the Tie2 receptor, binding between APC and Tie2 is inhibited significantly irrespective of APC concentration Homo sapiens
physiological function Activated protein C (APC) is a vitamin K-dependent serine protease that plays a key role in the regulation of blood coagulation but also exerts a broad range of cytoprotective actions on endothelium including suppression of inflammation and stabilization of endothelial barrier function. Activated protein C (APC) is a natural anticoagulant with strong anti-inflammatory, anti-apoptotic, and barrier stabilizing properties. These cytoprotective properties of APC are thought to be exerted through its pathway involving the binding of APC to endothelial protein C receptor and cleavage of protease-activated receptors. APC enhances endothelial barrier integrity via a novel pathway, by binding directly to and activating Tie2, a transmembrane endothelial tyrosine kinase receptor. After binding, APC rapidly activates Tie2 to enhance endothelial barrier function. APC-mediated cytoprotective signaling requires endothelial protein C receptor (EPCR) and cleavage of protease-activated receptor (PAR)1 at Arg46, which may occur in caveolin-1-enriched lipid rafts. In addition, other receptors, such as sphingosine-1-phosphate receptor 1 (S1P1), epidermal growth factor receptor (EGFR), PAR3, and Tie2, may independently or co-operatively contribute to APC-mediated protective effects on endothelium. For example, APC protects against endothelial barrier disruption by cross-activating S1P1 or by stimulating Ang1 whilst inhibiting Ang2 to activateTie2, both these mechanisms require signaling through EPCR and PAR1. APC rapidly suppresses endothelial permeability via Tie2. APC signals through Tie2 to reverse vascular leakage in vivo. Tie2-I alone does not affect EBA leakage into the kidneys or lungs. The protective effect of APC is significantly reversed by Tie2-I in all experiments Homo sapiens