Reactome | Phosphorylation of PD-1

Phosphorylation of PD-1

Stable Identifier

R-HSA-389762

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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The cytoplasmic domain of PD-1 features two critical tyrosine-based motifs: the Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) and the Immunoreceptor Tyrosine-based Switch Motif (ITSM). Upon engagement with its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), PD-1 becomes phosphorylated at tyrosine residues 223 and 248 within these motifs. This phosphorylation is catalyzed by kinases such as Lck and Csk, which bind to these motifs and are likely involved in initiating and regulating the phosphorylation of PD-1. These phosphorylation events are crucial for recruiting downstream signaling molecules that mediate PD-1’s inhibitory effects on T cell activation and immune response (Sheppard 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
18173375	PD-1 and its ligands in tolerance and immunity Keir, ME, Butte, MJ, Freeman, GJ, Sharpe, AH	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