Difference between revisions of "Part:BBa K4175003"
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<partinfo>BBa_K4175003 short</partinfo>
 
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This part is the intracellular domain of human programmed death-1 (PD-1). Expressed on effector T cells, PD-1 acts as an inhibitory receptor regulating T cell effector functions. When programmed death-ligand 1 (PD-L1) and PD-L2 on the antigen-presenting cells (APCs) bind to PD-1, the intracellular domain of PD-1 will recruit phosphatases including SHP2 to downregulate some signaling pathways (e.g., PI3K-AKT pathway). Consequently, the effector T cell activity is inhibited [1].
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This part is the intracellular domain of human programmed death-1 (PD-1) (aa 191-289).
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===Usage and Biology===
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<span class='h3bb'>Sequence and Features</span>
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===Sequence and Features===
 
<partinfo>BBa_K4175003 SequenceAndFeatures</partinfo>
 
<partinfo>BBa_K4175003 SequenceAndFeatures</partinfo>
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===Biology===
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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).
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Revision as of 14:24, 8 October 2022


human intracellular PD-1

This part is the intracellular domain of human programmed death-1 (PD-1) (aa 191-289).


Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE 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).