ArticleMolecular and cellular biology2009
Fibroblast growth factor receptor 3 associates with and tyrosine phosphorylates p90 RSK2, leading to RSK2 activation that mediates hematopoietic transformation.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Unleashing the potential of combining FGFR inhibitor and immune checkpoint blockade for FGF/FGFR signaling in tumor microenvironment.Molecular cancer · 2023Review
- RSK Isoforms in Acute Myeloid Leukemia.Biomedicines · 2021Review
- Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling.Cells · 2021Review
- Current challenges to underpinning the genetic basis for cholangiocarcinoma.Expert review of gastroenterology & hepatology · 2021Review
- Review
- Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment.International journal of molecular sciences · 2020Review
- RSK inhibitor BI-D1870 inhibits acute myeloid leukemia cell proliferation by targeting mitotic exit.Oncotarget · 2020Article
- Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML.Oncology letters · 2018Article
- Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis.Cell death & disease · 2018Article
- Review
- Bacterial Expression, Purification and In Vitro Phosphorylation of Full-Length Ribosomal S6 Kinase 2 (RSK2).PloS one · 2016Article
- Inhibition of RSK with the novel small-molecule inhibitor LJI308 overcomes chemoresistance by eliminating cancer stem cells.Oncotarget · 2015Article
- FGF10: Type III Epithelial Mesenchymal Transition and Invasion in Breast Cancer Cell Lines.Journal of Cancer · 2014Article
- p90 RSK2 mediates antianoikis signals by both transcription-dependent and -independent mechanisms.Molecular and cellular biology · 2013Article
- The unusual mechanism of inhibition of the p90 ribosomal S6 kinase (RSK) by flavonol rhamnosides.Biochimica et biophysica acta · 2013Review
- Identification of quercitrin as an inhibitor of the p90 S6 ribosomal kinase (RSK): structure of its complex with the N-terminal domain of RSK2 at 1.8 Å resolution.Acta crystallographica. Section D, Biological crystallography · 2013Article
- Article
- Analogs of the RSK inhibitor SL0101: optimization of in vitro biological stability.Bioorganic & medicinal chemistry letters · 2012Article
- FGF receptor inhibitors: role in cancer therapy.Current oncology reports · 2012Review
- p90RSK2 is essential for FLT3-ITD- but dispensable for BCR-ABL-induced myeloid leukemia.Blood · 2011Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Dysregulation of the receptor tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) plays a pathogenic role in a number of human hematopoietic malignancies and solid tumors. These include t(4;14) multiple myeloma associated with ectopic expression of FGFR3 and t(4;12)(p16;p13) acute myeloid leukemia associated with expression of a constitutively activated fusion tyrosine kinase, TEL-FGFR3. We recently reported that FGFR3 directly tyrosine phosphorylates RSK2 at Y529, which consequently regulates RSK2 activation. Here we identified Y707 as an additional tyrosine in RSK2 that is phosphorylated by FGFR3. Phosphorylation at Y707 contributes to RSK2 activation, through a putative disruption of the autoinhibitory alphaL-helix on the C terminus of RSK2, unlike Y529 phosphorylation, which facilitates ERK binding. Moreover, we found that FGFR3 interacts with RSK2 through residue W332 in the linker region of RSK2 and that this association is required for FGFR3-dependent phosphorylation of RSK2 at Y529 and Y707, as well as the subsequent RSK2 activation. Furthermore, in a murine bone marrow transplant assay, genetic deficiency in RSK2 resulted in a significantly delayed and attenuated myeloproliferative syndrome induced by TEL-FGFR3 as compared with wild-type cells, suggesting a critical role of RSK2 in FGFR3-induced hematopoietic transformation. Our current and previous findings represent a paradigm for tyrosine phosphorylation-dependent regulation of serine-threonine kinases.
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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.