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Literature summary for 3.4.21.69 extracted from

  • Xue, M.; Chow, S.O.; Dervish, S.; Chan, Y.K.; Julovi, S.M.; Jackson, C.J.
    Activated protein C enhances human keratinocyte barrier integrity via sequential activation of epidermal growth factor receptor and Tie2 (2011), J. Biol. Chem., 286, 6742-6750.
    View publication on PubMedView publication on EuropePMC
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens APC activates Tie2, a tyrosine kinase receptor, not through its major ligand, angiopoietin-1, but instead by binding to endothelial protein C receptor, cleaving protease-activated receptor-1 and transactivating EGF receptor ?
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 ?
protease-activated receptor-1 + H2O Homo sapiens
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 ?
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 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
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-
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Source Tissue

Source Tissue Comment Organism Textmining
keratinocyte adult skin cells and cells isolated from neonatal foreskins Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information APC activates Tie2, a tyrosine kinase receptor, not through its major ligand, angiopoietin-1, but instead by binding to endothelial protein C receptor, cleaving protease-activated receptor-1 and transactivating EGF receptor Homo sapiens ?
-
 ?
protease-activated receptor-1 + H2O
-
 Homo sapiens ?
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 ?

Synonyms

Synonyms Comment Organism
Activated protein C
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 Homo sapiens
APC
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 Homo sapiens

General Information

General Information Comment Organism
physiological function activated protein C is a natural anticoagulant with anti-inflammatory and endothelial barrier protective properties, which significantly increases the barrier impedance of keratinocyte monolayers, overview. APC also increases junction proteins zona occludens, claudin-1 and VE-cadherin. APC activates Tie2, via a mechanism requiring, in sequential order, the receptors, endothelial protein C receptor, protease activated receptor-1, and EGF receptor, which selectively enhances the PI3K/Akt signaling to enhance junctional complexes and reduce keratinocyte permeability. Inhibition of Tie2 by its peptide inhibitor or small interfering RNA abolishes the barrier protective effect of APC on keratinocytes, as well as inhibition of the activation of Akt, but not ERK Homo sapiens