The Ability of SOCS1 to Cross-Regulate GM-CSF Signaling is Dose Dependent
- Author(s)
- Bidgood, GM; Keating, N; Meza Guzman, L; Li, K; Leong, E; Kueh, A; Babon, JJ; Hockings, C; Doggett, K; Nicholson, SE;
- Journal Title
- Journal of Interferon & Cytokine Research
- Abstract
- Suppressor of cytokine signaling (SOCS) 1 is a key negative regulator of interferon (IFN), interleukin (IL)12, and IL-2 family cytokine signaling through inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. To investigate the temporal induction of SOCS1 in response to cytokine in live cells and its selective regulation of signaling pathways, we generated a mouse expressing a Halo-tag-SOCS1 fusion protein (Halo-SOCS1) under control of the endogenous Socs1 promoter. Homozygous Halo-SOCS1 mice (Halo-Socs1(KI/KI)) were viable with minor T cell abnormalities, most likely due to enhanced Halo-SOCS1 expression in thymocytes compared with the untagged protein. IFNγ and IL-4 induced Halo-SOCS1 expression in macrophages derived from Halo-Socs1(KI/KI) mice, and a critical level of SOCS1 expression was required for inhibition of both IFNγ and granulocyte macrophage-colony stimulating factor (GM-CSF)-driven JAK-STAT signaling. In contrast, IFNγ priming to induce SOCS1 did not cross-regulate IL-4 signaling. This study indicates that while SOCS1 expression needs to exceed a critical threshold to inhibit IFNγ signaling, its selective regulation of cytokine signaling results from an as yet undetermined, level of regulatory control.
- Publisher
- Mary Ann Liebert
- Keywords
- Gm-csf; Jak-stat; Socs1; interferon; signaling
- Research Division(s)
- Inflammation; Blood Cells and Blood Cancer; Structural Biology
- PubMed ID
- 39787022
- Publisher's Version
- https://doi.org/10.1089/jir.2024.0140
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-02-07 11:22:04
Last Modified: 2025-02-07 11:24:04