DAP12 信号传导
中文名称
通路描述
在受体结合后，DAP12 免疫受体酪氨酸基激活基序 (ITAM) 中的酪氨酸残基由Src 家族激酶磷酸化。这些磷酸化酪氨酸成为髓系细胞中蛋白酪氨酸激酶 SYK 的结合位点，以及 NK 细胞中 SYK 和 ZAP70 的结合位点。DAP12 结合的 SYK 自磷酸化并磷酸化支架分子 LAT，招募近端信号分子磷脂酰肌醇-3-OH 激酶 (PI3K)、磷脂酶 C gamma (PLC-gamma)、GRB2:SOS (Growth factor receptor-bound protein 2:Son of sevenless homolog 1)、SLP76 (SH2 结构域含 76 kDa 的白细胞蛋白) 和 GRB2:SOS。所有这些中间信号分子导致 AKT、CBL (Casitas B-lineage lymphoma) 和 ERK (细胞外信号调节激酶) 的招募和激活，以及肌动蛋白细胞骨架的重排 (肌动蛋白聚合)，最终导致细胞激活。PLC-gamma 产生次级信使二酰甘油 (DAG) 和肌醇-1,4,5-三磷酸 (InsP3)，分别激活蛋白激酶 C (PKC) 和钙动员 (Turnbull & Colonna 2007, Klesney-Tait et al. 2006)。
英文描述
DAP12 signaling 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).
所含基因
23 个基因