ArticleThe Biochemical journal2014
Mechanistic insights into activation and SOCS3-mediated inhibition of myeloproliferative neoplasm-associated JAK2 mutants from biochemical and structural analyses.
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Molecular Profile of BCR-ABL1 Negative Myeloproliferative Neoplasm in a Moroccan Population.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Emerging functions of pseudoenzymes.The Biochemical journal · 2023Review
- Article
- JAK1 Pseudokinase V666G Mutant Dominantly Impairs JAK3 Phosphorylation and IL-2 Signaling.International journal of molecular sciences · 2023Article
- Pseudokinase NRP1 facilitates endocytosis of transferrin in the African trypanosome.Scientific reports · 2022Article
- JAK2 in Myeloproliferative Neoplasms: Still a Protagonist.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms.International journal of molecular sciences · 2022Review
- Molecular pathogenesis of the myeloproliferative neoplasms.Journal of hematology & oncology · 2021Review
- Janus Kinases in Leukemia.Cancers · 2021Review
- Article
- Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association.Nature communications · 2017Article
- Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase.Frontiers in endocrinology · 2017Review
- The evolving world of pseudoenzymes: proteins, prejudice and zombies.BMC biology · 2016Article
- Uncoupling JAK2 V617F activation from cytokine-induced signalling by modulation of JH2 αC helix.The Biochemical journal · 2016Article
- Article
- Structural Basis for the Non-catalytic Functions of Protein Kinases.Structure (London, England : 1993) · 2016Review
- JAK2 activation by growth hormone and other cytokines.The Biochemical journal · 2015Review
- The molecular regulation of Janus kinase (JAK) activation.The Biochemical journal · 2014Review
- A new mechanism for growth hormone receptor activation of JAK2, and implications for related cytokine receptors.JAK-STAT · 2014Review
- There's more to death than life: Noncatalytic functions in kinase and pseudokinase signaling.The Journal of biological chemistryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
JAK2 (Janus kinase 2) initiates the intracellular signalling cascade downstream of cell surface receptor activation by cognate haemopoietic cytokines, including erythropoietin and thrombopoietin. The pseudokinase domain (JH2) of JAK2 negatively regulates the catalytic activity of the adjacent tyrosine kinase domain (JH1) and mutations within the pseudokinase domain underlie human myeloproliferative neoplasms, including polycythaemia vera and essential thrombocytosis. To date, the mechanism of JH2-mediated inhibition of JH1 kinase activation as well as the susceptibility of pathological mutant JAK2 to inhibition by the physiological negative regulator SOCS3 (suppressor of cytokine signalling 3) have remained unclear. In the present study, using recombinant purified JAK2JH1-JH2 proteins, we demonstrate that, when activated, wild-type and myeloproliferative neoplasm-associated mutants of JAK2 exhibit comparable enzymatic activity and inhibition by SOCS3 in in vitro kinase assays. SAXS (small-angle X-ray scattering) showed that JAK2JH1-JH2 exists in an elongated configuration in solution with no evidence for interaction between JH1 and JH2 domains in cis. Collectively, these data are consistent with a model in which JAK2's pseudokinase domain does not influence the activity of JAK2 once it has been activated. Our data indicate that, in the absence of the N-terminal FERM domain and thus cytokine receptor association, the wild-type and pathological mutants of JAK2 are enzymatically equivalent and equally susceptible to inhibition by SOCS3.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.