CoChat
Sign Up
PreprintCited by 1Cytokine Signaling Pathways and Interactionsinterferon and immune responsesProtein Tyrosine Phosphatases

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

ARAP2 regulates responses to interferon-gamma by restricting SOCS1

Open access
Keating, Narelle, Doggett, Karen, Bidgood, Grace M, Meza Guzman, Lizeth G, Dagley, Laura F, Li, Kunlun, Gabrielyan, Anna, Alvarado, Carolina, Williams, Bailey E, Broomfield, Benjamin J, Duckworth, Brigette C, Hockings, Colin, Yousef, Jumana, Leong, Evelyn, Morris, Rhiannon, Kueh, Andrew, Garnham, Alexandra L, Casanova, Jean-Laurent, Boisson-Dupuis, Stephanie, Babon, Jeffrey J, Linossi, Edmond M, Tate, Michelle D, Groom, Joanna R, Nicholson, Sandra E·2025·Cell Reports
DOI 10.1101/2025.04.28.650977

Preprint — published as 10.1016/j.celrep.2025.116667 · Paper page

Open this paper in CoChat — free account

Abstract

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 a potent immune response. Excessive JAK-STAT signaling can drive hyperinflammation and autoimmunity, and thus signaling is tightly and selectively regulated by the IFNγ-inducible protein, Suppressor of Cytokine Signaling 1 (SOCS1). SOCS1 inhibits signaling by directly blocking JAK kinase activity. Here we identified a SOCS1-interacting partner, ARAP2 that fine-tunes SOCS1 function. We report that tyrosine 415 in ARAP2 binds the SOCS1-Src Homology 2 (SH2) domain and limits the ability of SOCS1 to inhibit IFNγ signaling. Our findings show that ARAP2 promotes the IFNγ response through a phosphorylation dependent interaction with the negative regulator SOCS1.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2025.04.28.650977

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 76

  1. 10.1126/science.adl2016 · DOI
  2. 10.1038/nri1264 · DOI
  3. 10.1016/j.cell.2022.07.004 · DOI
  4. 10.1084/jem.178.6.2243 · DOI
  5. 10.1086/338002 · DOI
  6. 10.1128/iai.64.12.5151-5160.1996 · DOI
  7. 10.1016/1074-7613(95)90163-9 · DOI
  8. 10.1084/jem.179.4.1367 · DOI
  9. 10.1128/IAI.66.4.1708-1717.1998 · DOI
  10. Beer J , et al. Impaired immune response drives age-dependent severity of COVID-19. J Exp Med 219, (2022). · DOI
  11. 10.1128/JVI.72.8.6637-6645.1998 · DOI
  12. 10.3389/fimmu.2021.680334 · DOI
  13. 10.1038/43213 · DOI · Paper page
  14. 10.1038/43219 · DOI · Paper page
  15. 10.1073/pnas.95.24.14395 · DOI
  16. 10.1016/S0092-8674(00)80047-1 · DOI · Paper page
  17. 10.1016/S1074-7613(01)00132-7 · DOI
  18. Gruber C , et al. IL4Ralpha and IL17A Blockade Rescue Autoinflammation in SOCS1 Haploinsufficiency. J Clin Immunol 44, 36 (2023). · DOI
  19. 10.1038/s41467-020-18925-4 · DOI · Paper page
  20. 10.1007/s10875-022-01346-x · DOI
  21. 10.1016/j.jaci.2020.07.033 · DOI
  22. 10.1038/s41586-020-2265-1 · DOI
  23. 10.1016/j.jaut.2023.103119 · DOI
  24. 10.1016/S0021-9258(17)36621-8 · DOI
  25. 10.1146/annurev.iy.11.040193.003035 · DOI
  26. 10.1074/jbc.270.29.17528 · DOI
  27. 10.1002/j.1460-2075.1994.tb06422.x · DOI · Paper page
  28. 10.1016/1074-7613(95)90012-8 · DOI
  29. 10.1016/0092-8674(94)90357-3 · DOI · Paper page
  30. 10.1126/science.1496401 · DOI · Paper page
  31. 10.1126/science.1281555 · DOI
  32. 10.1126/science.7690989 · DOI · Paper page
  33. 10.1128/MCB.22.16.5662-5668.2002 · DOI · Paper page
  34. 10.1016/S1074-7613(03)00322-4 · DOI · Paper page
  35. 10.1038/ni1287 · DOI
  36. 10.1074/jbc.M117.788877 · DOI
  37. 10.1038/43206 · DOI · Paper page
  38. 10.1073/pnas.96.5.2071 · DOI
  39. 10.1073/pnas.231486498 · DOI
  40. 10.1038/nsmb.2519 · DOI · Paper page
  41. 10.1038/s41467-018-04013-1 · DOI · Paper page
  42. 10.1093/emboj/18.5.1309 · DOI · Paper page
  43. 10.1016/j.cyto.2023.156167 · DOI
  44. 10.1093/nar/gks1215 · DOI · Paper page
  45. 10.1016/j.coi.2010.06.003 · DOI
  46. 10.1016/j.virol.2018.10.017 · DOI
  47. 10.1038/mi.2017.41 · DOI
  48. 10.1016/j.celrep.2022.110456 · DOI
  49. 10.3389/fimmu.2024.1419951 · DOI
  50. 10.1016/S1097-2765(02)00428-8 · DOI
  51. 10.1242/jcs.03237 · DOI
  52. 10.1074/jbc.R300026200 · DOI
  53. 10.1074/jbc.M114.596155 · DOI
  54. 10.1371/journal.pgen.1002234 · DOI
  55. 10.1016/j.jmb.2009.01.024 · DOI
  56. Williams JJL , et al. Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability. Nat Commun 9, 168 (2018). · DOI · Paper page
  57. 10.1038/s41467-021-26983-5 · DOI
  58. 10.1002/art.41906 · DOI
  59. 10.1016/j.bcp.2022.115162 · DOI
  60. 10.1126/science.8456300 · DOI
  61. Delconte RB , et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nature Immunology, 816 (2016). · DOI
  62. 10.1093/emboj/18.2.375 · DOI · Paper page
  63. 10.1016/j.xpro.2020.100152 · DOI
  64. 10.1016/0076-6879(91)01043-2 · DOI · Paper page
  65. 10.1074/jbc.272.2.843 · DOI
  66. 10.1038/nmeth.1322 · DOI · Paper page
  67. 10.1021/pr101065j · DOI
  68. 10.1038/nbt.1511 · DOI · Paper page
  69. 10.1038/ni.3470 · DOI
  70. 10.1074/mcp.M114.041012 · DOI
  71. 10.1093/nar/gkae1011 · DOI
  72. 10.1128/JVI.00291-10 · DOI
  73. 10.1093/bioinformatics/btw777 · DOI · Paper page
  74. 10.1038/s41590-018-0276-y · DOI · Paper page
  75. 10.1038/s41586-018-0590-4 · DOI · Paper page
  76. 10.1038/nbt.4091 · DOI · Paper page

Metadata

Authors
Keating, N., Doggett, K., Bidgood, G. M., Meza Guzman, L. G., Dagley, L. F., Li, K., Gabrielyan, A., Alvarado, C., Williams, B. E., Broomfield, B. J., Duckworth, B. C., Hockings, C., Yousef, J., Leong, E., Morris, R., Kueh, A., Garnham, A. L., Casanova, J.-L., Boisson-Dupuis, S., Babon, J. J., Linossi, E. M., Tate, M. D., Groom, J. R., & Nicholson, S. E.
Affiliations
  • The University of Melbourne (AU)
  • Walter and Eliza Hall Institute of Medical Research, Melbourne, 3052, Australia
  • Hôpital Necker-Enfants Malades (FR)
  • St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
  • University of California, San Francisco (US)
  • Hudson Institute of Medical Research (AU)
Corresponding author
Nicholson, Sandra E
ORCID
Venue
Cell Reports
Publisher
openRxiv
Published
2025-04-29
Volume
44
Issue
12
Pages
116667-116667
ISSN
2211-1247 (ISSN-L)
DOI
10.1101/2025.04.28.650977
OpenAlex
W4417312873
Cited by
1
References
1
Citations by year
2026: 1
FWCI
0.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
Funders
  • Fulbright Association
  • University of Melbourne (GNT2007812)
  • State Government of Victoria
  • National Health and Medical Research Council (1121755, 2011761)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
SOCS1, interferon-gamma signaling, JAK/STAT signaling, tyrosine phosphorylation, negative regulation of cytokine signaling, influenza, inflammation, macrophages, autoimmunity
MeSH terms
Suppressor of Cytokine Signaling 1 Protein, Animals, Humans, Interferon-gamma, Mice, Inbred C57BL, Orthomyxoviridae Infections, Phosphorylation, Protein Binding, Signal Transduction, src Homology Domains, Adaptor Proteins, Signal Transducing, Mice, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review