Reactome | AMP-activated protein kinase (AMPK), activated in response t...

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created	[InstanceEdit:9937963] Tiwari, Krishna, 2025-02-10
dbId	9937966
displayName	AMP-activated protein kinase (AMPK), activated in response t...
literatureReference	[LiteratureReference:9935388] Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1 [LiteratureReference:9935371] Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade
modified	[InstanceEdit:9962761] Gillespie, Marc E, 2025-08-08
schemaClass	Summation
text	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).

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