NKG2D Signaling Enhances NK Cell Responses

NKG2D is an activating receptor, which is mainly expressed on cytotoxic immune cells. The protein has low homology with NKG2C and NKG2A. NKG2D plays a vital role in the identification and elimination of potentially dangerous cells. It has been shown to mediate immune responses against tumors, virus-infected cells, and organ transplants.

The ligands of NKG2D (NKG2DL) are induced-self proteins that are normally in low abundance but can be induced on the surface of stressed, malignant transformed, senescent, and infected cells. The NKG2D ligands are a family of molecules with structural similarity to MHC class I proteins, including human MICA/MICB and mouse RAE-1. These ligands represent a variety of sequences, yet all bind with NKG2D with high affinity.

NKG2D functions as a key receptor for NK cells as they conduct tumor surveillance. With very short intracellular domains, NKG2D has no signaling properties. In mice, NKG2D uses adaptor molecules DAP10 and DAP12 to relay its signal transduction, while in humans, NKG2D associates exclusively with DAP10. DAP10 and DAP12 initiate different signaling cascades. DAP10 possesses the YXXM motif, which functions to recruit PI3K and GRB2, activates the Rac1/PAK/c-RAF/MEK/ERK and GrB2/VAV-1 pathways, and finally induces NK cells exerting cytotoxic effects, releasing cytokines, and killing tumor cells via perforin/granzymes, TNF-αlpha/TNFR1, and Fas/Fas Ligand. DAP12 contains an immunoreceptor tyrosine-based activation motif (ITAM), which functions to recruit spleen tyrosine kinase (Syk) and zeta-chain-associated protein kinase 70 (ZAP70) to induce cytotoxicity and cytokine release.

NKG2D\NKG2DL may have applications as targets for effective antitumor therapy. The deviation of the ratio of NKG2D/NKG2DL from normal values can promote the escape of tumors from NK cell-mediated immune surveillance. Therefore, maximizing the activation of NKG2D expression on immune cells and fully inducing the expression of NKG2DL in tumor cells have become core concepts in cancer research.

Recombinant NKG2D Proteins

Validated Binding Activity

Human NKG2D (Cat#: 10575-H01S)
 

Bind with Human MICA 
(Cat#: 12302-H08H)
Human NKG2D (Cat#: 10575-H07B)
 

  • Bind with Human ULBP1
    (Cat#: 10679-H03H)

  • Bind with Human ULBP6
    (Cat#: 15759-H02H)
  • List of Recombinant NKG2D

    • Cat#: 10575-H01S
      Tag: Fc
      Purity: 95% (SDS-PAGE)
      Activity: Validated
    • Cat#: 10575-H07B
      Tag: His
      Purity: 90% (SDS-PAGE)
      Activity: Validated
    • Cat#: 57340-M01B
      Tag: Fc
      Purity: 90% (SDS-PAGE)
      Activity: Testing in progress
    • Cat#: 90164-C07B
      Tag: His
      Purity: 95% (SDS-PAGE)
      Activity: Testing in progress

    Note: H: Human; M: Mouse; Rh: Rhesus

    Recombinant NKG2D Ligands

    NKG2D ligands belong to the ULBP (ULBP1-ULBP6) and MIC (MICA and MICB) families in humans, and to the five different isoforms of the Rae1-family (α-ε), three different isoforms of H60 (a-c), and MULT1 in mice. Their sequences, domain compositions are diverse, yet all bind with high affinity to NKG2D. Sino Biological has developed a panel of high purity and high binding activity recombinant NKG2D ligands with multiple tags.

    MHC Class I Chain-related Proteins (MICs)

    MICA

    • Human MICA
      (Cat#: HPLC-12302-H08H)

      >95% as determined by SEC-HPLC
    • 12302-H02H
      Tag: Fc
      Purity: 90% (SDS-PAGE)
      Activity: Testing in progress
      12302-H08H1
      Tag: His
      Purity: 95% (SDS-PAGE)
      Activity: Validated
    • 12302-H08H
      Tag: His
      Purity: 97% (SDS-PAGE)
      Activity: Validated
      90924-C08H
      Tag: His
      Purity: 95% (SDS-PAGE)
      Activity: Testing in progress

    MICB

    • 10759-H03H
      Tag: Fc & His
      Purity: 98% (SDS-PAGE)
      Activity: Validated
    • 10759-H08H
      Tag: His
      Purity: 98% (SDS-PAGE)
      Activity: Validated

    Note: H: Human; Cy: Cynomolgus

    Human UL16-binding Proteins (ULBPs)

    Molecule   Cat#   Tag   Purity (SDS-PAGE)   Activity
     
    ULBP1   10679-H03H   Fc & His   95%   Validated
     
      10679-H08H   His   98%   Validated
     
      10679-H27H-B   AVI & His   95%   Validated
     
    ULBP2   12143-H02H   Fc   95%   Testing in progress
     
      12143-H08H   His   97%   Testing in progress
     
      12143-H27H-B   AVI & His   95%   Testing in progress
     
    ULBP4   16073-H02H   Fc   90%   Testing in progress
     
      16073-H08H   His   80%   Testing in progress
     
    ULBP6/RAET1L   15759-H02H   Fc   90%   Validated
     
      15759-H08H   His   95%   Testing in progress

    Poster of TNF Signaling Pathway