ArticleMolecular and cellular biology1998
Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 325 citations in OpenAlex.
- Article
- Fibroblast growth factor receptor substrate 2 interactome mapping reveals novel candidate interactors associated with migration and invasion.Cell communication and signaling : CCS · 2026Article
- A hotspot phosphorylation site on SHP2 drives oncoprotein activation and drug resistance.Nature communications · 2026Article
- Targeting Kinase Suppressor of Ras 1 (KSR1) for Cancer Therapy.Pharmaceutics · 2025Review
- A Hotspot Phosphorylation Site on SHP2 Drives Oncoprotein Activation and Drug Resistance.Research square · 2025Article
- A Hotspot Phosphorylation Site on SHP2 Drives Oncoprotein Activation and Drug Resistance.bioRxiv : the preprint server for biology · 2025Article
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- The roles of FGFR3 and c-MYC in urothelial bladder cancer.Discover oncology · 2024Review
- Article
- Formyl-peptide receptor 2 signalling triggers aerobic metabolism of glucose through Nox2-dependent modulation of pyruvate dehydrogenase activity.Open biology · 2023Article
- Medicinal chemistry perspective of pyrido[2,3-RSC advances · 2023Review
- Targeting RAS mutants in malignancies: successes, failures, and reasons for hope.Cancer communications (London, England) · 2023Review
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Receptor tyrosine kinases regulate signal transduction through a liquid-liquid phase separated state.Molecular cell · 2022Article
- Signaling Pathway and Small-Molecule Drug Discovery of FGFR: A Comprehensive Review.Frontiers in chemistry · 2022Review
- Review
- Accessory proteins of the RAS-MAPK pathway: moving from the side line to the front line.Communications biology · 2021Review
- Review
- Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling.Cells · 2021Review
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FRS2 is a lipid-anchored docking protein that plays an important role in linking fibroblast growth factor (FGF) and nerve growth factor receptors with the Ras/mitogen-activated protein (MAP) kinase signaling pathway. In this report, we demonstrate that FRS2 forms a complex with the N-terminal SH2 domain of the protein tyrosine phosphatase Shp2 in response to FGF stimulation. FGF stimulation induces tyrosine phosphorylation of Shp2, leading to the formation of a complex containing Grb2 and Sos1 molecules. In addition, a mutant FRS2 deficient in both Grb2 and Shp2 binding induces a weak and transient MAP kinase response and fails to induce PC12 cell differentiation in response to FGF stimulation. Furthermore, FGF is unable to induce differentiation of PC12 cells expressing an FRS2 point mutant deficient in Shp2 binding. Finally, we demonstrate that the catalytic activity of Shp2 is essential for sustained activation of MAP kinase and for potentiation of FGF-induced PC12 cell differentiation. These experiments demonstrate that FRS2 recruits Grb2 molecules both directly and indirectly via complex formation with Shp2 and that Shp2 plays an important role in FGF-induced PC12 cell differentiation.
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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.