Reactome | NEK2 phosphorylates CD274

NEK2 phosphorylates CD274

Stable Identifier

R-HSA-9931409

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane

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)
        
        GSK3B-mediated proteasomal degradation of PD-L1(CD274) (Homo sapiens)
        
        NEK2 phosphorylates CD274 (Homo sapiens)

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Never in mitosis gene A-related kinase 2 (NEK2) phosphorylates PD-L1 (CD274) at T194 and T210 residues and maintain its stability by preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in the ER lumen. A NEK binding motif (F/LXXS/T) was identified in the glycosylation-rich region of PD-L1 (Zhang et al, 2021).

Literature References

PubMed ID	Title	Journal	Year
34315872	NEK2 inhibition triggers anti-pancreatic cancer immunity by targeting PD-L1 Zhang, X, Huang, X, Xu, J, Li, E, Lao, M, Tang, T, Zhang, G, Guo, C, Zhang, X, Chen, W, Yadav, DK, Bai, X, Liang, T	Nat Commun	2021