ArticleOncogene2001
The insulin receptor substrate (IRS)-1 recruits phosphatidylinositol 3-kinase to Ret: evidence for a competition between Shc and IRS-1 for the binding to Ret.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 67 citations in OpenAlex.
- Hydroalcoholic Extracts ofMolecules (Basel, Switzerland) · 2026Article
- Personalized Medicine in Medullary Thyroid Carcinoma: A Broad Review of Emerging Treatments.Journal of personalized medicine · 2023Review
- RET aberrant cancers and RET inhibitor therapies: Current state-of-the-art and future perspectives.Pharmacology & therapeutics · 2023Review
- The role of the ShcD and RET interaction in neuroblastoma survival and migration.Biochemistry and biophysics reports · 2018Article
- Exon Skipping in the RET Gene Encodes Novel Isoforms That Differentially Regulate RET Protein Signal Transduction.The Journal of biological chemistry · 2016Article
- PI3K/Akt/mTOR signaling in medullary thyroid cancer: a promising molecular target for cancer therapy.Endocrine · 2015Review
- The Novel Functions of High-Molecular-Mass Complexes Containing Insulin Receptor Substrates in Mediation and Modulation of Insulin-Like Activities: Emerging Concept of Diverse Functions by IRS-Associated Proteins.Frontiers in endocrinology · 2015Review
- Central role of RET in thyroid cancer.Cold Spring Harbor perspectives in biology · 2013Review
- Thyroid Cancer: Role of RET and Beyond.European thyroid journal · 2012Review
- XB130, a tissue-specific adaptor protein that couples the RET/PTC oncogenic kinase to PI 3-kinase pathway.Oncogene · 2009Article
- Article
- Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2.Molecular and cellular biology · 2006Article
- Screening for PTB domain binding partners and ligand specificity using proteome-derived NPXY peptide arrays.Molecular and cellular biology · 2006Article
- Differential requirement of Tyr1062 multidocking site by RET isoforms to promote neural cell scattering and epithelial cell branching.Oncogene · 2004Article
- A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia.Molecular and cellular biology · 2004Article
- Protein kinase Calpha activation by RET: evidence for a negative feedback mechanism controlling RET tyrosine kinase.Oncogene · 2003Article
- The neuron-specific Rai (ShcC) adaptor protein inhibits apoptosis by coupling Ret to the phosphatidylinositol 3-kinase/Akt signaling pathway.Molecular and cellular biology · 2002Article
- RET/PTC1 oncogene signaling in PC Cl 3 thyroid cells requires the small GTP-binding protein Rho.Oncogene · 2001Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine 1062 of Ret, which represents an intracytoplasmic docking site for multiple signaling molecules, is essential for Ret-mediated activation of phosphatidylinositol 3-Kinase (PI3-K). PI3-K, in turn, has been implicated in inducing cell survival and neoplastic transformation mediated by Ret. We have examined the mechanisms by which Ret stimulates PI3-K. Here we show that the Insulin Receptor Substrate-1 (IRS-1) is tyrosine phosphorylated and associated with the p85 regulatory subunit of PI3-K in response to Ret activation. IRS-1 coimmunoprecipitates with Ret and co-expression of IRS-1 results in the potentiation of Ret-mediated activation of Akt(PKB), a bona fide effector of PI3-K. The association with the PTB domain of IRS-1 depends on the phosphorylation of tyrosine 1062 of Ret. The deletion of asparagine 1059 (delN1059) and the substitution of leucine 1061 (L1061P), two Ret mutations identified in families affected by congenital megacolon (Hirschsprung's disease), impair the binding of IRS-1 to Ret as well as Ret-mediated Akt(PKB) stimulation. Finally, we show that Shc, which was previously identified as another ligand of Y1062 of Ret, competes with IRS-1 for the binding to Ret pY1062. All together, these findings suggest that IRS-1 is a component of the signaling pathway which leads to Ret-mediated PI3-K activation, a pathway which can be targeted by Hirschsprung-associated Ret mutations. The alternative binding of Shc and IRS-1 to Ret pY1062 can be a system to modulate the activation of different intracellular signaling pathways and to elicit different biological responses following Ret activation.
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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.