The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Cytokine‐inducible SH2 protein‐3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N‐terminal kinase inhibitory region as well as SH2 domain
Open accessAbstract
Background: The Janus family of protein tyrosine kinases (JAKs) regulate cellular processes involved in cell growth, differentiation and transformation through their association with cytokine receptors. We have recently identified the JAK‐binding protein, JAB that inhibits various cytokine‐dependent JAK signalling pathways. JAB inhibits JAK2 tyrosine kinase activity by binding to the kinase domain (JH1 domain) through the N‐terminal kinase inhibitory region (KIR) and the SH2 domain. The SH2 domain of JAB has been shown to bind to the phosphorylated Y1007 in the activation loop of JH1. We also identified another JAK‐binding protein, CIS3 (cytokine‐inducible SH2‐protein 3, or SOCS3) that inhibits signalling of various cytokines. However, the mechanism of JAK signal inhibition by CIS3 has not been clarified. Results: We showed that endogenous CIS3 bound to JAK2 in intact cells. The CIS3‐SH2 domain bound to the phosphorylated Y1007 of JH1, and inhibited tyrosine kinase activity through the N‐terminal KIR. Therefore, CIS3 and JAB inhibit JAK2 tyrosine kinase activity by an essentially similar mechanism. However, we found that the affinity of the SH2 domain of CIS3 to Y1007 was weaker than that of JAB. In contrast, the KIR of CIS3 showed stronger potential for both binding to JH1 and inhibition of JAK kinase activity than that of JAB. Consistent with this notion, chimeras containing CIS3‐KIR and JAB‐SH2 domain inhibited JAK2 kinase activity more efficiently than the wild‐type CIS3 or JAB. Conclusion: CIS3 inhibits JAK2 kinase activity by binding to the activation loop through the SH2 domain, and KIR is necessary for kinase inhibition. Although the inhibitory mechanism by CIS3 is similar to that by JAB, the contributions of the SH2 domain and KIR for binding are different between JAB and CIS3. Our study defined the inhibitory mechanism of CIS3 and provides a useful information for creating a novel tyrosine kinase inhibitor.
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.
Integrity signals
Registry
Cites
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The suppressor of cytokine signaling (SOCS) family of proteins, especially SOCS1 and SOCS3, inhibit STAT3 in a cytokine-inducible manner by binding to and inhibiting upstream JAKs.13,14”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [13]
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
Darnell, J. E. (1997) · Science · doi:10.1126/science.277.5332.1630 · Cited by 3,979
A family of cytokine-inducible inhibitors of signalling
Starr, R., Willson, T. A., Viney, E. M., Murray, L. J. L., Rayner, J. R., Jenkins, B. J., Gonda, T. J., Alexander, W. S., Metcalf, D., Nicola, N. A., et al. (1997) · Nature · doi:10.1038/43206 · Cited by 2,066
A new protein containing an SH2 domain that inhibits JAK kinases
Endo, T. A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., et al. (1997) · Nature · doi:10.1038/43213 · Cited by 1,408
Self-citationSTATs: Signal Transducers and Activators of Transcription
Ihle, J. N. (1996) · Cell · doi:10.1016/s0092-8674(00)81277-5 · Cited by 1,381
Ihle, J. N. (1995) · Nature · doi:10.1038/377591a0 · Cited by 1,201
Structure and function of a new STAT-induced STAT inhibitor
Naka, T., Narazaki, M., Hirata, M., Matsumoto, T., Minamoto, S., Aono, A., Nishimoto, N., Kajita, T., Taga, T., Yoshizaki, K., et al. (1997) · Nature · doi:10.1038/43219 · Cited by 1,040
Identification of SOCS-3 as a Potential Mediator of Central Leptin Resistance
Bjørbæk, C., Elmquist, J. K., Frantz, J. D., Shoelson, S. E., & Flier, J. S. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80062-3 · Cited by 1,014
Yoshimura, A., Ohkubo, T., Kiguchi, T., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Hara, T., & Miyajima, A. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07281.x · Cited by 751
Self-citationCrystal Structure of a Tyrosine Phosphorylated STAT-1 Dimer Bound to DNA
Chen, X., Vinkemeier, U., Zhao, Y., Jeruzalmi, D., Darnell, J. E., Jr., & Kuriyan, J. (1998) · Cell · doi:10.1016/s0092-8674(00)81443-9 · Cited by 734
Twenty proteins containing a C-terminal SOCS box form five structural classes
Hilton, D. J., Richardson, R. T., Alexander, W. S., Viney, E. M., Willson, T. A., Sprigg, N. S., Starr, R., Nicholson, S. E., Metcalf, D., & Nicola, N. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.114 · Cited by 728
Cited by
Sorted by citations
Principles of interleukin (IL)-6-type cytokine signalling and its regulation
HEINRICH, P. C., BEHRMANN, I., HAAN, S., HERMANNS, H. M., MÜLLER-NEWEN, G., & SCHAPER, F. (2003) · Biochemical Journal · doi:10.1042/bj20030407 · Cited by 3,272
SOCS proteins, cytokine signalling and immune regulation
Yoshimura, A., Naka, T., & Kubo, M. (2007) · Nature Reviews Immunology · doi:10.1038/nri2093 · Cited by 1,580
Self-citationProtein Tyrosine Kinase Structure and Function
Hubbard, S. R., & Till, J. H. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.373 · Cited by 1,176
Mechanisms of leptin action and leptin resistance.
Myers, M. G., Cowley, M. A., & Münzberg, H. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.113006.100707 · Cited by 1,074
The role of JAK/STAT signaling pathway and its inhibitors in diseases.
Xin, P., Xu, X., Deng, C., Liu, S., Wang, Y., Zhou, X., Ma, H., Wei, D., & Sun, S. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106210 · Cited by 1,010
Metadata
- Authors
- Sasaki, A., Yasukawa, H., Suzuki, A., Kamizono, S., Syoda, T., Kinjyo, I., Sasaki, M., Johnston, J. A., & Yoshimura, A.
- Affiliations
- Kurume University (JP)
- Corresponding author
- Yoshimura, Akihiko
- Venue
- Genes to Cells
- Publisher
- Wiley
- Published
- 1999-06
- Volume
- 4
- Issue
- 6
- Pages
- 339-351
- ISSN
- 1356-9597 (ISSN-L)
- 1365-2443
- OpenAlex
- W2008295144
- Cited by
- 398
- References
- 28
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 13 · 2021: 13 · 2020: 13 · 2019: 17 · 2018: 15 · 2017: 15 · 2016: 8 · 2015: 17 · 2014: 19 · 2013: 18 · 2012: 29
- FWCI
- 5.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes to Cells (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Naito Foundation
- Sumitomo Foundation
- Kanae Foundation for the Promotion of Medical Science
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- SOCS3, JAK2, SH2 domain, jab, cytokine signaling, protein tyrosine kinase inhibitors, fusion protein
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Amino Acid Sequence, Enzyme Activation, Humans, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Transcription Factors, Signal Transduction, src Homology Domains, Suppressor of Cytokine Signaling Proteins, Janus Kinase 2
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
