PD-1 is conserved from sharks to humans: new insights into PD-1, PD-L1, PD-L2, and SHP-2 evolution.

ABSTRACT: Programmed cell death protein 1 (PD-1) is an immune checkpoint molecule until recently believed to exist only in tetrapod species. However, together with a very recent study dedicated to the CD28/CTLA4 molecule family, this study-using database information-identifies the PD-1 gene in both bony and cartilaginous fish, while being the first to present a detailed molecular analysis of the evolution of PD-1 and its ligands. Conserved sequence motifs imply an ancient origin of PD-1's binding modes to its extracellular ligand PD-L1 and its intracellular ligand Src homology region 2 domain-containing phosphatase-2 (SHP-2), and also of its N116 glycosylation motif-a less well known PD-1 feature-important for binding galectins. The PD-1 cytoplasmic tail binds SHP-2 by two motifs, defined as

SUBMITTER: Kondo R 

PROVIDER: S-EPMC12151841 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature