ArticleBlood2012
Adaptor protein Lnk binds to and inhibits normal and leukemic FLT3.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Secondary lesions and sensitivity to signaling inhibitors in iAMP21 acute lymphoblastic leukemia.HemaSphere · 2025Article
- Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.The Journal of experimental medicine · 2024Article
- A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia.International journal of molecular sciences · 2023Article
- LNK (SH2B3) inhibition expands healthy and Fanconi anemia human hematopoietic stem and progenitor cells.Blood advances · 2022Article
- The Role of LNK (SH2B3) in the Regulation of JAK-STAT Signalling in Haematopoiesis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Structural and functional analysis of target recognition by the lymphocyte adaptor protein LNK.Nature communications · 2021Article
- Transcriptional Regulation of Genes by Ikaros Tumor Suppressor in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Review
- SH2B3 inactivation through CN-LOH 12q is uniquely associated with B-cell precursor ALL with iAMP21 or other chromosome 21 gain.Leukemia · 2019Article
- FLT3-ITD and its current role in acute myeloid leukaemia.Medical oncology (Northwood, London, England) · 2017Review
- Article
- LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors.The Journal of clinical investigation · 2016Article
- Expression of GADS enhances FLT3-induced mitogenic signaling.Oncotarget · 2016Article
- The role of small adaptor proteins in the control of oncogenic signalingr driven by tyrosine kinases in human cancer.Oncotarget · 2016Review
- FYN expression potentiates FLT3-ITD induced STAT5 signaling in acute myeloid leukemia.Oncotarget · 2016Article
- BEX1 acts as a tumor suppressor in acute myeloid leukemia.Oncotarget · 2015Article
- LNK (SH2B3): paradoxical effects in ovarian cancer.Oncogene · 2015Article
- SOCS proteins in regulation of receptor tyrosine kinase signaling.Cellular and molecular life sciences : CMLS · 2014Review
- The genomic landscape of nasopharyngeal carcinoma.Nature genetics · 2014Article
- Article
- Grb10 is a dual regulator of receptor tyrosine kinase signaling.Molecular biology reports · 2014Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase with important roles in hematopoietic progenitor cell survival and proliferation. It is mutated in approximately one-third of AML patients, mostly by internal tandem duplications (ITDs). Adaptor protein Lnk is a negative regulator of hematopoietic cytokine signaling. In the present study, we show that Lnk interacts physically with both wild-type FLT3 (FLT3-WT) and FLT3-ITD through the SH2 domains. We have identified the tyrosine residues 572, 591, and 919 of FLT3 as phosphorylation sites involved in direct binding to Lnk. Lnk itself was tyrosine phosphorylated by both FLT3 ligand (FL)-activated FLT3-WT and constitutively activated FLT3-ITD. Both shRNA-mediated depletion and forced overexpression of Lnk demonstrated that activation signals emanating from both forms of FLT3 are under negative regulation by Lnk. Moreover, Lnk inhibited 32D cell proliferation driven by different FLT3 variants. Analysis of primary BM cells from Lnk-knockout mice showed that Lnk suppresses the expansion of FL-stimulated hematopoietic progenitors, including lymphoid-primed multipotent progenitors. The results of the present study show that through direct binding to FLT3, Lnk suppresses FLT3-WT/ITD-dependent signaling pathways involved in the proliferation of hematopoietic cells. Therefore, modulation of Lnk expression levels may provide a unique therapeutic approach for FLT3-ITD-associated hematopoietic disease.
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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.