Targets Associated to Immuno Cell Types - Natural killer cells

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The Natural killer cells category includes the following Cell Ontology parent terms:

natural killer cell (CL:0000623) - A lymphocyte that can spontaneously kill a variety of target cells without prior antigenic activation via germline encoded activation receptors and also regulate immune responses via cytokine release and direct contact with other cells.

GPCRs
GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
A2A receptor
(Adenosine receptors)
A2A receptor has non-specific association to Natural Killer cells.
  • non-specified (GTOIMMUPDB_DEFAULT_CELL:4)
A2A receptor is discussed in this immuno-oncology review [2] ...
5-HT1A receptor
(5-Hydroxytryptamine receptors)
    The chemoattractant properties of 5-HT on both human and mouse mast cells are mediated by 5-HT1A receptor [24] ...
    CXCR3
    (Chemokine receptors)
    • natural killer cell (CL:0000623)
    CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes.
    GPR65
    (Class A Orphans)
    • natural killer cell (CL:0000623)
    Tha expression profile of GPR65 suggests an immunological role. In addition, disruption of GPR65 expression leads to reduced eosinophilia in models of allergic airway disease [23] ...
    Enzymes
    GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
    FYN proto-oncogene, Src family tyrosine kinase
    (Src family)
    • natural killer cell (CL:0000623)
    Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [33] ...
    LCK proto-oncogene, Src family tyrosine kinase
    (Src family)
    • natural killer cell (CL:0000623)
    Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [33] ...
    LYN proto-oncogene, Src family tyrosine kinase
    (Src family)
    • natural killer cell (CL:0000623)
    LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [13,16,39] ...
    YES proto-oncogene 1, Src family tyrosine kinase
    (Src family)
    Low expression level
    • natural killer cell (CL:0000623)
    Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system.
    cathepsin C
    (C1: Papain)
    • natural killer cell (CL:0000623)
    Cathepsin C is a lysosomal cysteine protease constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, catheposin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (g ...
    Catalytic Receptors
    GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
    colony stimulating factor 1 receptor
    (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
    Down-regulated expression measured by Affymetrix GeneChip array, in experiments designed to expand NK cell populations as a potential cancer immunotherapy tool.
      Activation of the CSF1R induces myeloid proliferation, and in the tumour microenvironment this promotes M1 to M2 polarization and accumulation of tumour-associated macrophages (TAMs). The CSF1R is therefore being investigated as an immuno-oncology drug target [2] ...
      MER proto-oncogene, tyrosine kinase
      (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
      • natural killer cell (CL:0000623)
      Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [7,43] ...
      Other Protein Targets
      GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
      CD2
      (CD molecules)
        CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [44] ...
        CS1 (CD319)
        (CD molecules)
        • natural killer cell (CL:0000623)
        CS1 is a member of the signalling lymphocyte activation molecule (SLAM) receptor family. CS1 is a membrane glycoprotein primarily expressed on plasma cells. Homophilic interaction (i.e. interaction with itself) of CS1 induces B cell proliferation and autocrine cytokine secretion, thus playing a role in various immune functions.

        CS1 is a validated molecular target for the development of novel immunotherapeutics with the potential to treat MM, a malignant disease of plasma cells which remains incurable despite advances in treatment (such as bortezomib, lenalidomide and immunotherapies in clinical trial). Indeed, a combination therapy containing the anti-CS1 mAb elotuzumab (elotuzumab + lenalidomide + dexamethasone), was FDA approved for MM in 2015. CS1 expression is also elevated in patients with systemic lupus erythematosus (SLE) [22] ...
        CD38
        (CD molecules)
          CD38 is a type II transmembrane glycoprotein, widely expressed on immune cells and involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [19] ...
          CD52
          (CD molecules)
            CD52 (CAMPATH-1) is a short, glycosylphosphatidylinositol (GPI) anchored peptide expressed on lymphocytes and by cells of the male genital tract. CD52 is required for complement-mediated cell lysis and antibody-mediated cellular cytotoxicity. The approved monoclonal antibody, alemtuzumab ...
            neural cell adhesion molecule 1 (CD56)
            (CD molecules)
            • CD16-negative, CD56-bright natural killer cell (CL:0000938)
            CD56 is expressed by neurons, glia, skeletal muscle and natural killer (NK) cells. The CD56bright NK cell subset, predominantly present in secondary lymphoid tissues, are capable of high levels of cytokine production, are enriched at inflammatory sites [11] ...
            CD159a
            (CD molecules)
            • natural killer cell (CL:0000623)
            NKG2A (KLRC1; CD159a) acts as an inhibitory checkpoint receptor for HLA-E. NKG2A forms functional heterodimers with CD94 (KLRD1) to form a human leukocyte antigen E (HLA-E) recognition complex on a subset of natural killer (NK) cells and cytotoxic T cells. NKG2A/CD94/HLA-E binding suppresses immune vigilance, and overexpression of HLA-E is used by cancer cells to evade immune recognition and destruction [12,26,31,38] ...
            LAG3 (CD223)
            (CD molecules)
            LAG3 is expressed on activated human NK cells.
            • natural killer cell (CL:0000623)
            LAG3 (CD223) is a T cell inhibitory receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [3] ...
            programmed cell death 1 ligand 1 (CD274)
            (CD molecules)
              PD-L1 is an endogenous ligand of the checkpoint receptor programmed cell death 1 (PD-1). Engagement of PD-1 by PD-L1 has immunosuppressive action. Both the ligand and receptor are being pursued as targets for novel oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Antibody-based therapies targeting the PD-1/PD-L1 pathway augment immune responses and eliminate tumour-induced tolerance. Clinically this action has been observed as regression in various tumour types, including melanoma, renal cell carcinoma [32] ...
              CD300a
              (CD molecules)
              CD300a (IRp60) was originally identified in NK cells.
              • natural killer cell (CL:0000623)
              CD300a is a member of the CD300 family of leucocyte surface receptors [8] ...