Reactome: A Curated Pathway Database

DAP12 signaling (R-HSA-2424491)

Species Homo sapiens

Summation

In response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the docking site for the protein tyrosine kinase SYK in myeloid cells and SYK and ZAP70 in NK cells. DAP12-bound SYK autophosphorylates and phosphorylates the scaffolding molecule LAT, recruiting the proximal signaling molecules phosphatidylinositol-3-OH kinase (PI3K), phospholipase-C gamma (PLC-gamma), GADS (GRB2-related adapter downstream of SHC), SLP76 (SH2 domain-containing leukocyte protein of 76 kDa), GRB2:SOS (Growth factor receptor-bound protein 2:Son of sevenless homolog 1) and VAV. All of these intermediate signalling molecules result in the recruitment and activation of kinases AKT, CBL (Casitas B-lineage lymphoma) and ERK (extracellular signal-regulated kinase), and rearrangement of the actin cytoskeleton (actin polymerization) finally leading to cellular activation. PLC-gamma generates the secondary messengers diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (InsP3), leading to activation of protein kinase C (PKC) and calcium mobilization, respectively (Turnbull & Colonna 2007, Klesney-Tait et al. 2006).

Locations in the PathwayBrowser
Cross References
Database Identifier
BioModels Database BIOMD0000000175, BIOMD0000000468, BIOMD0000000424, BIOMD0000000255
Literature References
pubMedId Title Journal Year
17220916 Activating and inhibitory functions of DAP12 Nat. Rev. Immunol. 2007
17110943 The TREM receptor family and signal integration Nat Immunol 2006
15884055 KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions Eur J Immunol 2005