ArticleScience signaling2018
The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 56 citations in OpenAlex.
- Harnessing the murine inner cell mass mechanical environment enhances derivation of in vitro nascent primitive endoderm precursor cells.Development (Cambridge, England) · 2026Article
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Control-guided refinement of partially specified Boolean networks: applications to RTK signaling.Bioinformatics (Oxford, England) · 2026Article
- SHIP2-PLK1 crosstalk promotes sensitivity to dual inhibition in esophageal squamous cell carcinoma.Molecular cancer · 2025Article
- Therapeutic Prospects of αv Integrins Inhibition in Fibrotic Lung Diseases and Carcinogenesis.International journal of molecular sciences · 2025Review
- Cell expansion for notochord mechanics and endochondral bone lengthening in zebrafish depends on the 5'-inositol phosphatase Inppl1a.Current biology : CB · 2025Article
- Endoplasmic reticulum stress disrupts signaling via altered processing of transmembrane receptors.Cell communication and signaling : CCS · 2025Article
- Increased thermal stability of FGF10 leads to ectopic signaling during development.Cellular and molecular life sciences : CMLS · 2025Article
- Specific inhibition of fibroblast growth factor receptor 1 signaling by a DNA aptamer.Molecular therapy. Nucleic acids · 2025Article
- Maternal high glucose and fat diet exposure impaired vascular constriction via miR-325-3P/SHIP2/NOX2 pathway axis in offspring vessels.Cellular and molecular life sciences : CMLS · 2024Article
- Achondroplasia: aligning mouse model with human clinical studies shows crucial importance of immediate postnatal start of the therapy.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Article
- Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice.Nature communications · 2023Article
- Review
- Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling.Cells · 2021Review
- Molecular characterization of organoids derived from pancreatic intraductal papillary mucinous neoplasms.The Journal of pathology · 2020Article
- SHIP2 inhibition alters redox-induced PI3K/AKT and MAP kinase pathways via PTEN over-activation in cervical cancer cells.FEBS open bio · 2020Article
- Both Hypoxia-Inducible Factor 1 and MAPK Signaling Pathway Attenuate PI3K/AKT via Suppression of Reactive Oxygen Species in Human Pluripotent Stem Cells.Frontiers in cell and developmental biology · 2020Article
- Human Papillomavirus 11 Early Protein E6 Activates Autophagy by Repressing AKT/mTOR and Erk/mTOR.Journal of virology · 2019Article
- Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance.Cancer cell · 2019Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
Abstract
Sustained activation of extracellular signal-regulated kinase (ERK) drives pathologies caused by mutations in fibroblast growth factor receptors (FGFRs). We previously identified the inositol phosphatase SHIP2 (also known as INPPL1) as an FGFR-interacting protein and a target of the tyrosine kinase activities of FGFR1, FGFR3, and FGFR4. We report that loss of SHIP2 converted FGF-mediated sustained ERK activation into a transient signal and rescued cell phenotypes triggered by pathologic FGFR-ERK signaling. Mutant forms of SHIP2 lacking phosphoinositide phosphatase activity still associated with FGFRs and did not prevent FGF-induced sustained ERK activation, demonstrating that the adaptor rather than the catalytic activity of SHIP2 was required. SHIP2 recruited Src family kinases to the FGFRs, which promoted FGFR-mediated phosphorylation and assembly of protein complexes that relayed signaling to ERK. SHIP2 interacted with FGFRs, was phosphorylated by active FGFRs, and promoted FGFR-ERK signaling at the level of phosphorylation of the adaptor FRS2 and recruitment of the tyrosine phosphatase PTPN11. Thus, SHIP2 is an essential component of canonical FGF-FGFR signal transduction and a potential therapeutic target in FGFR-related disorders.
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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 Socratic graph.