Reactome | AMPK phosphorylates CD274

AMPK phosphorylates CD274

Stable Identifier

R-HSA-9931292

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, endoplasmic reticulum lumen

ReviewStatus

5/5

Locations in the PathwayBrowser

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Immune System (Homo sapiens)

- Adaptive Immune System (Homo sapiens)
  - Regulation of T cell activation by CD28 family (Homo sapiens)
    - Co-inhibition by PD-1 (Homo sapiens)
      - Regulation of PD-L1(CD274) expression (Homo sapiens)
        
        Regulation of PD-L1(CD274) Post-translational modification (Homo sapiens)
        
        AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) (Homo sapiens)
        
        AMPK phosphorylates CD274 (Homo sapiens)

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AMP-activated protein kinase (AMPK), activated in response to metformin, directly binds with PD-L1 (CD274) and phosphorylates S195 of PD-L1. This phosphorylation induces abnormal PD-L1 glycosylation (abnormal mannose trimming), resulting in its endoplasmic reticulum (ER) accumulation and ER-associated protein degradation (ERAD) (Cha et al., 2018, Dai et al., 2021). In addition to Ser195, AMPK phosphorylates Ser283 on PD-L1, which promotes its lysosome-mediated degradation (Dai et al., 2021).

Literature References

PubMed ID	Title	Journal	Year
33909988	Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade Dai, X, Bu, X, Gao, Y, Guo, J, Hu, J, Jiang, C, Zhang, Z, Xu, K, Duan, J, He, S, Zhang, J, Wan, L, Liu, T, Zhou, X, Hung, MC, Freeman, GJ, Wei, W	Mol Cell	2021
30118680	Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1 Cha, JH, Yang, WH, Xia, W, Wei, Y, Chan, LC, Lim, SO, Li, CW, Kim, T, Chang, SS, Lee, HH, Hsu, JL, Wang, HL, Kuo, CW, Chang, WC, Hadad, S, Purdie, CA, McCoy, AM, Cai, S, Tu, Y, Litton, JK, Mittendorf, EA, Moulder, SL, Symmans, WF, Thompson, AM, Piwnica-Worms, H, Chen, CH, Khoo, KH, Hung, MC	Mol Cell	2018