ArticleMolecular and cellular biology2001
Docking protein FRS2 links the protein tyrosine kinase RET and its oncogenic forms with the mitogen-activated protein kinase signaling cascade.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 140 citations in OpenAlex.
- Fibroblast growth factor receptor substrate 2 interactome mapping reveals novel candidate interactors associated with migration and invasion.Cell communication and signaling : CCS · 2026Article
- Targeting Kinase Suppressor of Ras 1 (KSR1) for Cancer Therapy.Pharmaceutics · 2025Review
- Personalized Medicine in Medullary Thyroid Carcinoma: A Broad Review of Emerging Treatments.Journal of personalized medicine · 2023Review
- RET signaling in breast cancer therapeutic resistance and metastasis.Breast cancer research : BCR · 2023Review
- Inhibition of FGF receptor blocks adaptive resistance to RET inhibition in CCDC6-RET-rearranged thyroid cancer.The Journal of experimental medicine · 2022Article
- PTPRA Phosphatase Regulates GDNF-Dependent RET Signaling and Inhibits the RET Mutant MEN2A Oncogenic Potential.iScience · 2020Article
- Akt-ing Up Just About Everywhere: Compartment-Specific Akt Activation and Function in Receptor Tyrosine Kinase Signaling.Frontiers in cell and developmental biology · 2019Review
- Overexpression of TFEB Drives a Pleiotropic Neurotrophic Effect and Prevents Parkinson's Disease-Related Neurodegeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes.Nature reviews. Clinical oncology · 2018Review
- Demonstration of a potent RET transcriptional inhibitor for the treatment of medullary thyroid carcinoma based on an ellipticine derivative.International journal of oncology · 2017Article
- Exon Skipping in the RET Gene Encodes Novel Isoforms That Differentially Regulate RET Protein Signal Transduction.The Journal of biological chemistry · 2016Article
- Genetic insights into the mechanisms of Fgf signaling.Genes & development · 2016Review
- Selective repression of RET proto-oncogene in medullary thyroid carcinoma by a natural alkaloid berberine.BMC cancer · 2015Article
- Article
- Central role of RET in thyroid cancer.Cold Spring Harbor perspectives in biology · 2013Review
- Mitogen-Activated Protein (MAP) Kinase Scaffolding Proteins: A Recount.International journal of molecular sciences · 2013Article
- Structure and physiology of the RET receptor tyrosine kinase.Cold Spring Harbor perspectives in biology · 2013Review
- Thyroid Cancer: Role of RET and Beyond.European thyroid journal · 2012Review
- Flotillin-1/reggie-2 protein plays dual role in activation of receptor-tyrosine kinase/mitogen-activated protein kinase signaling.The Journal of biological chemistry · 2012Article
- Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor tyrosine kinase RET functions as the signal transducing receptor for the GDNF (for "glial cell-derived neurotrophic factors") family of ligands. Mutations in the RET gene were implicated in Hirschsprung disease (HSCR), multiple endocrine neoplasia type 2 (MEN 2), and thyroid carcinomas. In this report we demonstrate that the docking protein FRS2 is tyrosine phosphorylated by ligand-stimulated and by constitutively activated oncogenic forms of RET. Complex formation between RET and FRS2 is mediated by binding of the phosphotyrosine-binding domain of FRS2 to pY1062, a residue in RET that also functions as a binding site for Shc. However, overexpression of FRS2 but not Shc potentiates mitogen-activated protein (MAP) kinase activation by RET oncoproteins. We demonstrate that oncogenic RET-PTC proteins are associated with FRS2 constitutively, leading to tyrosine phosphorylation of FRS2, MAP kinase stimulation, and cell proliferation. However, loss-of-function HSCR-associated RET mutants exhibit impaired FRS2 binding and reduced MAP kinase activation. These experiments demonstrate that FRS2 couples both ligand-regulated and oncogenic forms of RET, with the MAP kinase signaling cascade as part of the response of RET under normal biological conditions and pathological conditions, such as MEN 2 and papillary thyroid carcinomas.
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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.