Reactome | Dephosphorylation of CD3-zeta by PD-1 bound phosphatases

Dephosphorylation of CD3-zeta by PD-1 bound phosphatases

Stable Identifier

R-HSA-389758

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Dephosphorylation of CD3-zeta by PD-1 bound phosphatases

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PD-1 delivers inhibitory signals and downregulates antigen receptor signaling through the direct dephosphorylation of signaling intermediates. The phosphatases SHP-1 and SHP-2 play key roles in this process by dephosphorylating CD3ζ, which is a crucial component of the T cell receptor complex. This dephosphorylation inhibits the phosphorylation of downstream signaling molecules, including ZAP-70 and PKCθ, leading to impaired T cell activation and function. By regulating these signaling pathways, PD-1 helps maintain immune tolerance and modulate the immune response (Chemnitz 1 et al. 2004).

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
15358536	PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta Jussif, JM, Benander, C, Carter, LL, Wooters, J, Fitz, LJ, Qiu, Y, Chaudhary, D, George, JA, Sheppard, KA, Wood, CR, Lee, JM	FEBS Lett	2004
18173375	PD-1 and its ligands in tolerance and immunity Keir, ME, Sharpe, AH, Freeman, GJ, Butte, MJ	Annu Rev Immunol	2008
12947224	Cytotoxic T-lymphocyte antigen-4 and programmed death-1 function as negative regulators of lymphocyte activation Carter, LL, Carreno, BM	Immunol Res	2003