Tyrosine phosphatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal TH17 responses.
Zihou DengShixin MaHao ZhouAiping ZangYiyuan FangTiantian LiHuanjing ShiMei LiuMin DuPatricia R TaylorHelen He ZhuJiangye ChenGuangxun MengFubin LiChangbin ChenYan ZhangXin-Ming JiaXin LinXiaoming ZhangEric PearlmanXiaoxia LiGen-Sheng FengHui XiaoPublished in: Nature immunology (2015)
Fungal infection stimulates the canonical C-type lectin receptor (CLR) signaling pathway via activation of the tyrosine kinase Syk. Here we identify a crucial role for the tyrosine phosphatase SHP-2 in mediating CLR-induced activation of Syk. Ablation of the gene encoding SHP-2 (Ptpn11; called 'Shp-2' here) in dendritic cells (DCs) and macrophages impaired Syk-mediated signaling and abrogated the expression of genes encoding pro-inflammatory molecules following fungal stimulation. Mechanistically, SHP-2 operated as a scaffold, facilitating the recruitment of Syk to the CLR dectin-1 or the adaptor FcRγ, through its N-SH2 domain and a previously unrecognized carboxy-terminal immunoreceptor tyrosine-based activation motif (ITAM). We found that DC-derived SHP-2 was crucial for the induction of interleukin 1β (IL-1β), IL-6 and IL-23 and anti-fungal responses of the TH17 subset of helper T cells in controlling infection with Candida albicans. Together our data reveal a mechanism by which SHP-2 mediates the activation of Syk in response to fungal infection.
Keyphrases
- tyrosine kinase
- epidermal growth factor receptor
- dendritic cells
- candida albicans
- signaling pathway
- genome wide
- immune response
- high glucose
- gene expression
- regulatory t cells
- diabetic rats
- poor prognosis
- cell proliferation
- escherichia coli
- cell wall
- epithelial mesenchymal transition
- dna methylation
- binding protein
- deep learning
- electronic health record
- cystic fibrosis
- pi k akt
- oxidative stress
- transcription factor
- long non coding rna
- single cell
- staphylococcus aureus
- artificial intelligence
- endothelial cells
- endoplasmic reticulum stress