NKp30
| NKp30 | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 183 amino acids | |
| Secondary to quaternary structure | Type 1 transmembrane protein | |
| Isoforms | 6th | |
| Identifier | ||
| Gene names | NCR3 ; CD337 | |
| External IDs | ||
| Occurrence | ||
| Homology family | NCR3 | |
| Parent taxon | Higher mammals | |
NKp30 ( gene : NCR3 ), synonym CD337, is a receptor protein that is located in the cell membrane of natural killer cells in all higher mammals . NKp30 contributes to the ability of the killer cells to distinguish friend from foe (cell) and accordingly to slow down or ramp up the activity of the killer cell. People with a special change in the NCR3 gene show an increased susceptibility to malaria .
NKp30 is one of three known natural cytotoxic receptors .
physiology
With this receptor, NK cells recognize various (see above) target cells, are activated and destroy these target cells. This z. B. Cancer cells and cells infected with intracellular pathogens eliminated.
The interaction of NK cells with dendrite cells becomes interesting; the latter secrete exosomes with the target structure bat3 and express bat3 on their cell surface; The result is an activation of the NK cells which, through cytokine production, cause the differentiation of the dendrite cells from iDC to mDC and, through direct cytotoxicity, reduce the number of non-differentiating iDC. The mDC differentiated in this way will now induce adaptive immune reactions typical of TH1 .
Molecular structure
Extracellular (120 AA, V-type immunoglobulin like domain), transmembrane region (19 AA, one arginine, see ITAM binding), cytoplasmic (33 AA).
Target structures
- A first target antigen is BAT3 , this is an essential protein for the regulation of apoptosis , the function of which is still largely unknown.
- Malaria -infected erythrocytes, recognizes DBL-1alpha peptide of the malaria protein pfemp1.
- PP65 of cytomegalovirus binds (blocking) NKp30.
Cells expressing target structures
- Almost all cells and cell lines tested express NKp30-binding structures, both in a cellular compartment, which corresponds to an early endosome , and on the plasma membrane.
- Dendrite cells (immature iDC and mature mDC) secrete exosomes to which BAT3 is bound.
Signal transduction
NKp30 binds CD3ζ , via its ITAM motif the activation of the small tyrosine kinase syk , u. a. thereby the activation of the NFκB system via NIK . The consequences are NK proliferation , NK cytotoxicity and cytokine production, e.g. B. TNFα and IFNγ .
Expressing cells
Almost exclusively NK cells in all activation levels.
Individual evidence
- ↑ UniProt O14931
- ↑ Ferlazzo G. et al .: Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med 195 (3): 343-51 (2002) PMID 11828009
- ↑ Vitale M. et al .: NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor . Blood 106 (2): 566-71 (2005) PMID 15784725
- ↑ Pende D. et al .: Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J Exp Med 190 (10): 1505-16 (1999) PMID 10562324
- ↑ Pogge von Strandmann E. et al .: Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Immunity 27 (6): 965-74 (2007) PMID 18055229
- ↑ Simhadri VR. et al .: Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function . PLoS ONE 3 (10): e3377 (2008) PMID 18852879
- ↑ Sivaraman S. et al .: Inhibition of the bacterial enoyl reductase FabI by triclosan: a structure-reactivity analysis of FabI inhibition by triclosan analogues. J Med Chem 47 (3): 509-18 (2004) PMID 14736233
- ↑ Byrd A. et al .: Expression analysis of the ligands for the Natural Killer cell receptors NKp30 and NKp44. PLoS ONE 2 (12): e1339 (2007) PMID 18092004
- ↑ Pandey R. et al .: NKp30 ligation induces rapid activation of the canonical NF-kappaB pathway in NK cells. J Immunol 179 (11): 7385-96 (2007) PMID 18025182