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.
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.
Note: H: Human; Cy: Cynomolgus
|ULBP1||10679-H03H||Fc & His||95%||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|
|15759-H08H||His||95%||Testing in progress|