ArticleBlood2005
Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways.
Article in Blood, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Influence of Genetic Variants in EGF and Other Genes on Hematological Traits in Korean Populations by a Genome-Wide Approach.BioMed research international · 2015Pooled it
- Lnk Governs chemokine-directed trafficking of CD8Molecular therapy. Oncology · 2026Article
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- The LNK adaptor protein: a dual regulator of proliferation and migration in solid tumors.Molecular & cellular oncology · 2026Review
- LNK/SH2B3 Loss Exacerbates the Development of Myeloproliferative Neoplasms in CBL-deficient Mice.Stem cell reviews and reports · 2025Article
- LNK/Haematologica · 2024Article
- The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age.Mechanisms of ageing and development · 2024Article
- Article
- Biallelic deleterious germlineEJHaem · 2023Article
- HDAC6 regulates human erythroid differentiation through modulation of JAK2 signalling.Journal of cellular and molecular medicine · 2023Article
- Case report: Application of targeted NGS for the detection of non-canonical driver variants in MPN.Frontiers in genetics · 2023Article
- Genomic Aging, Clonal Hematopoiesis, and Cardiovascular Disease.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- A Single Nucleotide Polymorphism inCirculation research · 2022Article
- Immune dysregulation associated with co-occurring germline CBL and SH2B3 variants.Human genomics · 2022Article
- Genetic Background of Polycythemia Vera.Genes · 2022Review
- LNK (SH2B3) inhibition expands healthy and Fanconi anemia human hematopoietic stem and progenitor cells.Blood advances · 2022Article
- Antibodies of the immunoglobulin a isotype to novel antigens in early axial spondyloarthritis.Frontiers in medicine · 2022Article
- The Missing LNK: Evolution from Cytosis to Chronic Myelomonocytic Leukemia in a Patient with Multiple Sclerosis and Germline SH2B3 Mutation.Case reports in genetics · 2022Article
- The Role of LNK (SH2B3) in the Regulation of JAK-STAT Signalling in Haematopoiesis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Autoimmune Risk R262W Variant of the Adaptor SH2B3 Improves Survival in Sepsis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Erythropoietin (Epo), along with its receptor EpoR, is the principal regulator of red cell development. Upon Epo addition, the EpoR signaling through the Janus kinase 2 (JAK2) activates multiple pathways including Stat5, phosphoinositide-3 kinase (PI-3K)/Akt, and p42/44 mitogen-activated protein kinase (MAPK). The adaptor protein Lnk is implicated in cytokine receptor signaling. Here, we showed that Lnk-deficient mice have elevated numbers of erythroid progenitors, and that splenic erythroid colony-forming unit (CFU-e) progenitors are hypersensitive to Epo. Lnk(-/-) mice also exhibit superior recovery after erythropoietic stress. In addition, Lnk deficiency resulted in enhanced Epo-induced signaling pathways in splenic erythroid progenitors. Conversely, Lnk overexpression inhibits Epo-induced cell growth in 32D/EpoR cells. In primary culture of fetal liver cells, Lnk overexpression inhibits Epo-dependent erythroblast differentiation and induces apoptosis. Lnk blocks 3 major signaling pathways, Stat5, Akt, and MAPK, induced by Epo in primary erythroblasts. In addition, the Lnk Src homology 2 (SH2) domain is essential for its inhibitory function, whereas the conserved tyrosine near the C-terminus and the pleckstrin homology (PH) domain of Lnk are not critical. Furthermore, wild-type Lnk, but not the Lnk SH2 mutant, becomes tyrosine-phosphorylated following Epo administration and inhibits EpoR phosphorylation and JAK2 activation. Hence, Lnk, through its SH2 domain, negatively modulates EpoR signaling by attenuating JAK2 activation, and regulates Epo-mediated erythropoiesis.
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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.