Reactome | PIM1 phosphorylates GBP1

PIM1 phosphorylates GBP1

Stable Identifier

R-HSA-9954237

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Immune System (Homo sapiens)

- Cytokine Signaling in Immune system (Homo sapiens)
  - Interferon Signaling (Homo sapiens)
    - Antimicrobial mechanism of IFN-stimulated genes (Homo sapiens)
      - GBP-mediated host defense (Homo sapiens)
        
        Regulation of GBP-mediated host defense (Homo sapiens)
        
        PIM1 phosphorylates GBP1 (Homo sapiens)

General

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Proto-oncogene serine/threonine kinase 1 (PIM1) phosphorylates guanylate-binding protein 1 (GBP1) at Ser156 and Thr590. Phosphorylation at Ser156 promotes GBP1 binding to 14-3-3σ (SFN), which sequesters GBP1 in the cytosol and prevents its association with membranes. This inhibitory interaction is thought to suppress GBP1 activity in uninfected cells (Fisch D et al., 2023). The PIM1:GBP1 interaction has also been implicated in drug resistance in certain cancers, including ovarian cancer (De Donato M et al., 2012; Andreoli M et al., 2014). GTP binding to GBP1 disrupts its interaction with PIM1 through an allosteric mechanism (Persico M et al., 2015).

Literature References

PubMed ID	Title	Journal	Year
37797010	PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection Fisch, D, Pfleiderer, MM, Anastasakou, E, Mackie, GM, Wendt, F, Liu, X, Clough, B, Lara-Reyna, S, Encheva, V, Snijders, AP, Bando, H, Yamamoto, M, Beggs, AD, Mercer, J, Shenoy, AR, Wollscheid, B, Maslowski, KM, Galej, WP, Frickel, EM	Science	2023