A5038347519- Cytokine Signaling Pathways and Interactions
- Medicinal Plant Pharmacodynamics Research
- interferon and immune responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Protein Tyrosine Phosphatases
- Eosinophilic Esophagitis
- Chemical Synthesis and Analysis
- Whipple's Disease and Interleukins
- Tuberculosis Research and Epidemiology
- Reproductive System and Pregnancy
- Protein Kinase Regulation and GTPase Signaling
- RNA regulation and disease
- Biochemical and Molecular Research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Immunotherapy and Biomarkers
- Galectins and Cancer Biology
- IL-33, ST2, and ILC Pathways
- Mycobacterium research and diagnosis
Walter and Eliza Hall Institute of Medical Research
2017-2025
The University of Melbourne
2017-2025
Rockefeller University
2022-2024
Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and IL-12 IL-23 mycobacterial diseases). Cells common P1104A allele selectively impaired isolated disease). We report three new forms of deficiency six patients from five families (R864C, G996R, G634E, or G1010D) compound heterozygous a (A928V). All these missense encode detectable proteins. The R864C G1010D are...
The Suppressor of Cytokine Signaling (SOCS) family proteins are important negative regulators cytokine signaling. SOCS1 is the prototypical member SOCS and functions in a classic negative-feedback loop to inhibit signaling response interferon, interleukin-12 interleukin-2 cytokines. These cytokines have critical role orchestrating our immune defence against viral pathogens cancer. ability limit positions it as an checkpoint, evidenced by detection detrimental variants patients with...
Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder only tuberculosis
Suppressor of cytokine signaling (SOCS) 1 is a key negative regulator interferon (IFN), interleukin (IL)12, and IL-2 family through inhibition the Janus kinase-signal transducer activator transcription (JAK-STAT) pathway. To investigate temporal induction SOCS1 in response to live cells its selective regulation pathways, we generated mouse expressing Halo-tag-SOCS1 fusion protein (Halo-SOCS1) under control endogenous
Suppressor Of Cytokine Signaling (SOCS) 1 is a critical negative regulator of cytokine signaling and required to protect against an excessive inflammatory response. Genetic deletion Socs1 results in unrestrained neonatal lethality, characterised by immune infiltrate multiple organs. Overexpression structural studies have suggested that the SOCS1 kinase inhibitory region (KIR) Src homology 2 (SH2) domain are important for interaction with inhibition receptor-associated JAK1, JAK2 TYK2...
SUMMARY Interferon-gamma (IFNγ) is critical for immunity against intra-macrophagic pathogens, signaling through the JAK-STAT pathway to induce a tyrosine-phosphorylation cascade that ensures potent immune response. Excessive can drive hyperinflammation and autoimmunity, thus tightly selectively regulated by IFNγ-inducible protein, Suppressor of Cytokine Signaling 1 (SOCS1). SOCS1 inhibits directly blocking JAK kinase activity. Here we identified SOCS1-interacting partner, ARAP2 fine-tunes...
Suppressor of cytokine signaling (SOCS)2 protein is a key negative regulator the growth hormone (GH) and Janus kinase (JAK)-Signal Transducers Activators Transcription (STAT) cascade. The central SOCS2-Src homology 2 (SH2) domain characteristic SOCS family proteins an important module that facilitates recognition targets bearing phosphorylated tyrosine (pTyr) residues. Here we identify exosite on SOCS2-SH2 which, when bound to non-phosphorylated peptide (F3), enhances SH2 affinity for...
Abstract Protein Tyrosine Phosphatase 1B (PTP1B) is the prototypical protein tyrosine phosphatase and plays an essential role in regulation of several kinase-driven signalling pathways. PTP1B displays a preference for bisphosphorylated substrates. Here we identify as inhibitor IL-6 show that, vitro, it can dephosphorylate all four members JAK family. In order to gain detailed understanding molecular mechanism dephosphorylation, undertook structural biochemical analysis dephosphorylation...
Suppressor of cytokine signaling 1 (SOCS1) has emerged as a potential therapeutic target in inflammatory and viral diseases. SOCS1 operates via its kinase inhibitory region, Src homology 2 (SH2) domain, SOCS box to negatively regulate the Janus kinase/signal transducers activators transcription pathway. In this study, we utilized native phosphotyrosine peptide substrates starting point iteratively explore requirement each amino acid position SH2 domain SOCS1. We show that Met, Thr, Val, Asp...
Abstract Suppressor Of Cytokine Signaling (SOCS) 1 is a critical negative regulator of cytokine signaling and required to protect against an excessive inflammatory response. Genetic deletion Socs1 results in unrestrained neonatal lethality, characterised by immune infiltrate multiple organs. Overexpression structural studies have suggested that the SOCS1 kinase inhibitory region (KIR) Src homology 2 (SH2) domain are important for interaction with inhibition receptor-associated JAK1, JAK2...