Part:BBa_K4175003
human intracellular PD-1
This part is the intracellular domain of human programmed death-1 (PD-1) (aa 191-289).
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
Biology
PD-1 acts as an inhibitory ‘checkpoint’ upon T cell activation to prevent T cells from attacking healthy cells (Sharpe and Pauken, 2018). In the early phase of T cell activation, PD-1 is expressed on the membrane of effector T cells. When programmed death-ligand 1 (PD-L1) and PD-L2 on the antigen-presenting cells (APCs) bind to PD-1, the immunoreceptor tyrosine-based switch motif (ITSM) in the intracellular part of PD-1 will recruit phosphatases such as SHP2 (Fig 1). These phosphatases can then disturb the positive signal exerted by T cell receptors (TCR) by inhibiting ZAP70, and PI3K-AKT and RAS signaling pathway. Notably, the TCR signaling can only be inhibited by PD-1 when PD-L1 or PD-L2 is presented on the same cell where the antigen for TCR recognition is presented (Sharpe and Pauken, 2018). As a result, the activation of various transcriptional factors, such as AP-1, NFAT and NF-κB is decreased, leading to decreased T cell activation, proliferation and survival. It has also been found that PD-1 can trigger basic leucine zipper transcriptional factor ATF-like (BATF) activation, which has negative effect on TCR signaling (Sharpe and Pauken, 2018).
| biology | Human |