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DAP12 Target

Also showing Tyrobp Target

$305
100 µl
This Cell Signaling Technology antibody is conjugated to biotin under optimal conditions. The biotinylated antibody is expected to exhibit the same species cross-reactivity as the unconjugated DAP12 (D7G1X) Rabbit mAb #12492.
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: DNAX-activating protein 12 (DAP12, TYROBP) is a signaling adaptor for several pathogen receptors expressed by cells of the innate immune system (1). The DAP12 protein structure consists of a short extracellular domain, a transmembrane domain, and a cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM) (2). DAP12 protein is expressed by hematopoietic cells, including NK cells, monocytes, macrophages, dendritic cells, mast cells, basophils, eosinophils, neutrophils, and some γδ T cells and NKT cells (1). DAP12 exists as a homodimer that associates with a variety of receptors involved in pathogen detection, including the KIR family of NK cell receptors (2,3). Ligand binding by DAP12-associated receptors results in phosphorylation of tyrosine residues within the DAP12 ITAM by Src family kinases and leads to activation of Syk or Zap-70 and downstream signaling responses (2).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: DNAX-activating protein 12 (DAP12, TYROBP) is a signaling adaptor for several pathogen receptors expressed by cells of the innate immune system (1). The DAP12 protein structure consists of a short extracellular domain, a transmembrane domain, and a cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM) (2). DAP12 protein is expressed by hematopoietic cells, including NK cells, monocytes, macrophages, dendritic cells, mast cells, basophils, eosinophils, neutrophils, and some γδ T cells and NKT cells (1). DAP12 exists as a homodimer that associates with a variety of receptors involved in pathogen detection, including the KIR family of NK cell receptors (2,3). Ligand binding by DAP12-associated receptors results in phosphorylation of tyrosine residues within the DAP12 ITAM by Src family kinases and leads to activation of Syk or Zap-70 and downstream signaling responses (2).

Background: Microglia cells are resident macrophages of the brain that survey the brain environment and dynamically respond to maintain brain homeostasis. Microglial responses include phagocytosis of cellular debris, restricting sites injury or pathology, and/or releasing inflammatory signals to initiate an immune response. Such responses are important during normal development and during diseased states (1).Recently, the role of microglia in neurodegenerative disease pathology, particularly Alzheimer’s disease (AD), has been of intense investigation. Much of this work is driven by human genetic data that links microglia-enriched genes with AD progression (2). The triggering receptor expressed on myeloid cells 2 (TREM2) protein is an innate immune receptor that is expressed on the cell surface of microglia (3). TREM2 plays a role in innate immunity, and a rare functional variant (R47H) of the TREM2 gene is associated with the late-onset risk of AD (3,4). How TREM2 contributes to disease function is currently an active area of research (4,5), but might drive a number of microglial cellular functions ranging from microgliosis, phagocytosis, and cytokine release via a variety of signaling cascades triggered by TREM2.The TREM2 receptor is a single-pass type I membrane glycoprotein that consists of an extracellular immunoglobulin-like domain, a transmembrane domain, and a cytoplasmic tail. Ligands for TREM2 include phospholipids, apolipoproteins, and lipoproteins. Upon activation, TREM2 interacts with the tyrosine kinase-binding protein DNAX-activating protein 12 (DAP12, TYROBP) to form a receptor-signaling complex (6). Ligand binding by DAP12-associated receptors, including TREM2, results in phosphorylation of tyrosine residues within the DAP12 immunoreceptor tyrosine-based activation motif (ITAM) by Src family kinases; ITAM phosphorylation leads to activation of spleen tyrosine kinase (Syk) and downstream signaling cascades (7). Tyr525 and Tyr526 are located in the activation loop of the Syk kinase domain and phosphorylation at these residues (equivalent to Tyr519/520 of mouse Syk) is essential for Syk function (8). Syk phosphorylation is also a readout for β-amyloid triggered TREM2 activity (9). Phosphoinositide-specific phospholipase C γ 1/2 (PLCγ1/2) is reported to be down stream of Syk (10). Tyr352 of Syk is involved in the association of PLCγ1 (11); Syk-mediated phosphorylation PLCγ1 at Tyr783 activates PLCγ1 enzymatic activity (12). Interestingly, mutations in the microglia-enriched PLCγ2 gene are associated with AD (13,14,15).