DAP12 signaling

Stable Identifier
R-HSA-2424491
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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DAP12 signaling
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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).
Literature References
PubMed ID Title Journal Year
17220916 Activating and inhibitory functions of DAP12

Turnbull, IR, Colonna, M

Nat. Rev. Immunol. 2007
15884055 KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions

Tomasello, E, Vivier, E

Eur J Immunol 2005
17110943 The TREM receptor family and signal integration

Klesney-Tait, J, Turnbull, IR, Colonna, M

Nat Immunol 2006
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Orthologous Events
DAP12 signaling (Bos taurus)
DAP12 signaling (Canis familiaris)
DAP12 signaling (Drosophila melanogaster)
DAP12 signaling (Gallus gallus)
DAP12 signaling (Mus musculus)
DAP12 signaling (Rattus norvegicus)
DAP12 signaling (Sus scrofa)
DAP12 signaling (Xenopus tropicalis)
Cross References
BioModels Database
Authored
Garapati, P V  (2012-05-25)
Reviewed
Lanier, LL  (2012-08-09)
Created
Garapati, P V  (2012-07-23)
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