Interleukin‐3 stabilizes <scp>CD124</scp>/<scp>IL</scp>‐4α surface expression in mast cells via <scp>Tyk2</scp> and <scp>STAT6</scp>

Drube, Sebastian; Strotmann, Birgit; Wegner, Philine; Jäger, Ute; Küchler, Claudia; Andreas, Nico

doi:10.1111/imm.13614

Cited by 2 publications

(2 citation statements)

References 42 publications

(72 reference statements)

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“…The helix domain regulates the processes of nuclear import and export. [101][102][103][104] The DNA-binding domain enables STATs to bind DNA as transcription factors. 105 The SH2 domain recognizes phosphorylated tyrosine on specific cytokine receptors.…”

Section: Jak Stat and The Jak-stat Pathwaymentioning

confidence: 99%

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Xue

Yao

et al. 2023

Sig Transduct Target Ther

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The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes, including proliferation, metabolism, immune response, inflammation, and malignancy. Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and cancer progression. Insights into the structures and functions of the JAK-STAT pathway have led to the development and approval of diverse drugs for the clinical treatment of diseases. Currently, drugs have been developed to mainly target the JAK-STAT pathway and are commonly divided into three subtypes: cytokine or receptor antibodies, JAK inhibitors, and STAT inhibitors. And novel agents also continue to be developed and tested in preclinical and clinical studies. The effectiveness and safety of each kind of drug also warrant further scientific trials before put into being clinical applications. Here, we review the current understanding of the fundamental composition and function of the JAK-STAT signaling pathway. We also discuss advancements in the understanding of JAK-STAT–related pathogenic mechanisms; targeted JAK-STAT therapies for various diseases, especially immune disorders, and cancers; newly developed JAK inhibitors; and current challenges and directions in the field.

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Section: Jak Stat and The Jak-stat Pathwaymentioning

confidence: 99%

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Xue

Yao

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…MCs are located in peripheral tissues and are one part of the first line of defence in the immune system. Under physiological conditions the activation of MCs by the IgE/FcεRI axis or by alarmins such as IL-33 and/or ATP [10] in absence or presence of growth factors [11][12][13][14][15][16][17][18] results in degranulation and thus in the release of histimines and proteases as well as to the de novo synthesis of cytokines and chemokines which mediate neutrophile attraction of to the side of infection [13,19]. However, under pathophysiological conditions, the expression of constitutively active c-Kit mutants and/or of defective regulators of the transcription machinery results in the development of mastocytosis or MCs tumours [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

The Neurobeachin‐like 2 protein (NBEAL2) controls the homeostatic level of the ribosomal protein RPS6 in mast cells

Wegner,

Drube,

Ziegler

et al. 2024

Immunology

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The Beige and Chediak‐Higashi (BEACH) domain‐containing, Neurobeachin‐like 2 (NBEAL2) protein is a molecule with a molecular weight of 300 kDa. Inactivation of NBEAL2 by loss‐of‐function mutations in humans as well as deletion of the Nbeal2 gene in mice results in functional defects in cells of the innate immune system such as neutrophils, NK‐cells, megakaryocytes, platelets and of mast cells (MCs). To investigate the detailed function of NBEAL2 in murine MCs we generated MCs from wild type (wt) and Nbeal2−/− mice, and deleted Nbeal2 by CRISPR/Cas9 technology in the murine mast cell line MC/9. We also predicted the structure of NBEAL2 to infer its function and to examine potential mechanisms for its association with interaction partners by using the deep learning‐based method RoseTTAFold and the Pymol© software. The function of NBEAL2 was analysed by molecular and immunological techniques such as co‐immunoprecipitation (co‐IP) experiments, western blotting, enzyme‐linked immunosorbent assay and flow cytometry. We identified RPS6 as an interaction partner of NBEAL2. Thereby, the NBEAL2/RPS6 complex formation is probably required to control the protein homeostasis of RPS6 in MCs. Consequently, inactivation of NBEAL2 leads to accumulation of strongly p90RSK‐phosphorylated RPS6 molecules which results in the development of an abnormal MC phenotype characterised by prolonged growth factor‐independent survival and in a pro‐inflammatory MC‐phenotype.

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Interleukin‐3 stabilizes CD124/IL‐4α surface expression in mast cells via Tyk2 and STAT6

Cited by 2 publications

References 42 publications

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

The Neurobeachin‐like 2 protein (NBEAL2) controls the homeostatic level of the ribosomal protein RPS6 in mast cells

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