Skip to main content
. Author manuscript; available in PMC: 2018 Mar 1.
Published in final edited form as: Cancer Treat Rev. 2017 Feb 11;54:99–109. doi: 10.1016/j.ctrv.2017.01.009

Figure 2.

Figure 2

PD-1 and its downstream effect. Upon binding to ligands, PD-1’s ITIMs and ITSMs are phosphorylated by Src-family tyrosine kinases. The phosphorylated tyrosine residue subsequently recruits SHP-2 and SHP-1/SHP-2 in ITIM and ITSM, respectively. Activated PD-1 eventually hinders PI3K/Akt and RAS/MEK/ERK pathways, thwarts the function of PKC-θ and ZAP70 phosphorylation and inhibits glycolysis. The net effect is decreased cell cycle progression, IL-2 production, T-cell activation and effector T-cell development and increased apoptosis.

Src, Src-family tyrosine kinases; ITIM, immunoreceptor tyrosine-based inhibitory motif; ITSM, immunoreceptor tyrosine-based switch motif; P in red circle, phosphorylated tyrosine residues; SHP1 and SHP2, Src homology 2 domain-containing phosphatases, PI3K/Akt, Phosphatidylinositol-4,5-bisphosphate 3-kinase; Akt, Protein kinase B; PKC-θ, protein kinase C-theta; RAS/MEK/ERK, RAS/MEK/ERK pathway.