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Co-inhibition by PD-1
Stable Identifier
R-HSA-389948
Type
Pathway
Species
Homo sapiens
Compartment
plasma membrane
Synonyms
PD-1 signaling
ReviewStatus
5/5
Locations in the PathwayBrowser
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Immune System (Homo sapiens)
Adaptive Immune System (Homo sapiens)
Regulation of T cell activation by CD28 family (Homo sapiens)
Co-inhibition by PD-1 (Homo sapiens)
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Programmed cell death protein 1 (PD-1) is a crucial inhibitory receptor that regulates T cell receptor (TCR) signaling and plays a vital role in maintaining immune homeostasis. PD-1 exerts its suppressive effects both directly, by inhibiting early activation events that are otherwise enhanced by co-stimulatory signals like CD28, and indirectly, by reducing interleukin-2 (IL-2) production, which is essential for T cell proliferation and survival. Upon ligation, PD-1 inhibits the expression of key survival and differentiation factors, such as Bcl-xL, and downregulates transcription factors that are central to effector T cell function, including GATA-3, T-bet, and Eomes. Mechanistically, PD-1 recruits the tyrosine phosphatases SHP-1 and SHP-2 to the immune synapse, leading to the dephosphorylation of critical signaling molecules like the CD3-zeta chain, PI3K, and AKT, thereby attenuating TCR signaling and inhibiting T cell activation and function (Keir et al. 2008).
Literature References
PubMed ID
Title
Journal
Year
18759926
Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways
Fife, BT
,
Bluestone, JA
Immunol Rev
2008
18173375
PD-1 and its ligands in tolerance and immunity
Keir, ME
,
Sharpe, AH
,
Freeman, GJ
,
Butte, MJ
Annu Rev Immunol
2008
Participants
Events
PD-1 binds B7DC and B7H1
(Homo sapiens)
PDCD1 binds PDCD1 inhibitors
(Homo sapiens)
Phosphorylation of PD-1
(Homo sapiens)
Interaction of SHP-1 or SHP-2 with phospho PD-1
(Homo sapiens)
Dephosphorylation of CD3-zeta by PD-1 bound phosphatases
(Homo sapiens)
Participates
as an event of
Regulation of T cell activation by CD28 family (Homo sapiens)
Orthologous Events
Co-inhibition by PD-1 (Bos taurus)
Co-inhibition by PD-1 (Canis familiaris)
Co-inhibition by PD-1 (Gallus gallus)
Co-inhibition by PD-1 (Mus musculus)
Co-inhibition by PD-1 (Rattus norvegicus)
Co-inhibition by PD-1 (Sus scrofa)
Cross References
BioModels Database
BIOMD0000000724
Authored
Garapati, P V (2024-11-07)
Garapati, P V (2008-12-16)
Reviewed
D'Eustachio, P (2024-11-07)
Bluestone, JA (2009-06-01)
Esensten, J (2009-06-01)
Created
Garapati, P V (2009-01-21)
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