ArticleThe Journal of clinical investigation2012
14-3-3 regulates the LNK/JAK2 pathway in mouse hematopoietic stem and progenitor cells.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 26 citations in OpenAlex.
- 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
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- Modulation of JAK-STAT Signaling by LNK: A Forgotten Oncogenic Pathway in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2023Review
- HDAC6 regulates human erythroid differentiation through modulation of JAK2 signalling.Journal of cellular and molecular medicine · 2023Article
- Review
- Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice.Science translational medicine · 2022Article
- The Role of LNK (SH2B3) in the Regulation of JAK-STAT Signalling in Haematopoiesis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Compensatory Protection of Thioredoxin-Deficient Cells from Etoposide-Induced Cell Death by Selenoprotein W via Interaction with 14-3-3.International journal of molecular sciences · 2021Article
- HectD1 controls hematopoietic stem cell regeneration by coordinating ribosome assembly and protein synthesis.Cell stem cell · 2021Article
- Article
- SH2B3, Transcribed by STAT1, Promotes Glioblastoma Progression Through Transducing IL-6/gp130 Signaling to Activate STAT3 Signaling.Frontiers in cell and developmental biology · 2021Article
- Adaptor protein LNK promotes anaplastic thyroid carcinoma cell growth via 14-3-3 ε/γ binding.Cancer cell international · 2020Article
- LNK suppresses interferon signaling in melanoma.Nature communications · 2019Article
- Article
- The role of LNK/SH2B3 genetic alterations in myeloproliferative neoplasms and other hematological disorders.Leukemia · 2017Review
- CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies.Genes & development · 2017Article
- Specific disruption of Lnk in murine endothelial progenitor cells promotes dermal wound healing via enhanced vasculogenesis, activation of myofibroblasts, and suppression of inflammatory cell recruitment.Stem cell research & therapy · 2016Article
- The role of small adaptor proteins in the control of oncogenic signalingr driven by tyrosine kinases in human cancer.Oncotarget · 2016Review
- TRIM32 modulates pluripotency entry and exit by directly regulating Oct4 stability.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Hematopoietic stem and progenitor cell (HSPC) functions are governed by intricate signaling networks. The tyrosine kinase JAK2 plays an essential role in cytokine signaling during hematopoiesis. The adaptor protein LNK is a critical determinant of this process through its inhibitory interaction with JAK2, thereby limiting HSPC self-renewal. LNK deficiency promotes myeloproliferative neoplasm (MPN) development in mice, and LNK loss-of-function mutations are found in human MPNs, emphasizing its pivotal role in normal and malignant HSPCs. Here, we report the identification of 14-3-3 proteins as LNK binding partners. 14-3-3 interfered with the LNK-JAK2 interaction, thereby alleviating LNK inhibition of JAK2 signaling and cell proliferation. Binding of 14-3-3 required 2 previously unappreciated serine phosphorylation sites in LNK, and we found that their phosphorylation is mediated by glycogen synthase kinase 3 and PKA kinases. Mutations of these residues abrogated the interaction and augmented the growth inhibitory function of LNK. Conversely, forced 14-3-3 binding constrained LNK function. Furthermore, interaction with 14-3-3 sequestered LNK in the cytoplasm away from the plasma membrane-proximal JAK2. Importantly, bone marrow transplantation studies revealed an essential role for 14-3-3 in HSPC reconstitution that can be partially mitigated by LNK deficiency. We believe that, together, this work implicates 14-3-3 proteins as novel and positive HSPC regulators by impinging on the LNK/JAK2 pathway.
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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.