T cell receptor and co-stimulatory signaling (Homo sapiens)
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Description
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Ontology Terms
Saving...Bibliography
- Takahashi K, Yan I, Haga H, Patel T; ''Long non-coding RNA in liver diseases.''; Hepatology, 2014 PubMed Europe PMC Scholia
- Srikanth S, Gwack Y; ''Orai1-NFAT signalling pathway triggered by T cell receptor stimulation.''; Mol Cells, 2013 PubMed Europe PMC Scholia
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| Protein | |||
| CD28 | Protein | Cluster of Differentiation 28 | CD28 is a co-stimulatory surface receptor. It bind B7-1 and B7-2. After CD28 binds its ligand, it is phosphorylated by Lck. The effect of this phosphorylation activates P13K to generate PIP3 which recruits Itk to the cell membrane where Lck can phosphorylate it. Then Itk-P can recruit PLC-g |
| CTLA-4 | Protein | Cytotoxic T-lymphocyte-associated protein 4 | Expression is enhanced by IL-2.
Function is controlled largely by regulation of its surface expression. Initially CTLA-4 is in the intracellular membrane but moves to the cell surface after T-cell receptor signaling. When CTLA-4 cytoplasmic tail is NOT phosphorylated it binds to AP-2 (clathrin adapter molecule) and is removed from the surface. When the tail is phosphorylated AP-2 cannot bind and CTLA-4 is expressed on the surface. CTLA-4 competes with CD28 for B7 ligand, and it has a higher affinity of B7 in part because CTLA-4 binds B7 in a dimer. CTLA-4 interfers with the formation of lipid rafts, TCR:ZAP70 microclusters, and central supramolecular activation complex. |
| LAT | Protein | Linker for Activation of T cells | LAT is a transmembrane scaffold protein. It can be phosphorylated by Zap-70. |
| LcK | Protein | lymphcyte-specific protein tyrosine kinase | Cytoplasmic tyrosine kinase - Lck in its inactive state is bound to CD4/CD8 cytoplasmic tail and it's terminal tyrosine is phosphorylated. Dephosphorylation of this amino acid (by tyrosine phosphotase CD45 -- CD4/CD8 binding its ligand) causes a conformations change in LcK and it becomes an active tyrosine kinase.
LcK is activated when the extracellular part of CD8 binds its (MHC:peptide) ligand. Lck is a Src family kinase that is constitutively expressed. It phosphorylates all TCR ITAMS. Rephosphorylation of this carboxyl-terminal tyrosine by Csk returns Lck to the inactive state. Basically, Lck is bond to CD8. When CD8 binds MHC:peptide, Lck gets activated and can phosphorylate nearby ITAMs. |
| PD-1 | Protein | Programmed Cell Death 1 | PD-1 is repressed by pro-inflammatry cytokines. It's ligand, PD-L1, is constitutively expressed on T-cells. PD-1 contains a ITIM (immunoreceptor tyrosine-based inhibitory motif) in its cytoplasmic tail. When this ITIM is phosphorylated, it recruits either of 2 inhibitory phosphatases called SHP |
| SLP-76 | Protein | Lymphocyte cytosolic protein 2 (also known as LCP2) | An adapter, cytosolic protein that becomes linked to LAT (after they are both phosphorylated by Zap-70) through the adapter protein Gads. |
| TCR | Complex | T cell receptor complex | |
| Zap-70 | Protein | Zeta-chain-associated protein kinase 70 | ZAP-70 is kinase that becomes activated after phosphorylation. It contains to tandem SH2 domains that bind to phosphorylated ITAMs on the TCR complex cytoplasmic tails.
It docks at the TCR (requires both ITAM positions to be phosphorylated), is then phosphorylated by Lck, and then recruits other signaling proteins. |
Annotated Interactions
No annotated interactions
