ArticleProceedings of the National Academy of Sciences of the United States of America2004
The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor alpha to the plasma membrane.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed, 337 citations in OpenAlex.
- The influence of insulin-like Growth Factor-1-Receptor expression and endocrine treatment on clinical outcome of postmenopausal hormone receptor positive breast cancer patients: A Dutch TEAM substudy analysis.Molecular oncology · 2016Trial
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- Juvenile hormone induces phosphorylation of insulin/insulin-like growth factor signaling proteins in previtellogenic Aedes aegypti mosquitoes.Insect science · 2025Article
- Estrogenic control of matrix metalloproteinases: a perspective on breast tumor invasion and metastasis.Molecular biology reports · 2025Review
- Comparative study of dexamethasone premedication regimens with docetaxel chemotherapy in early HER-2 positive breast cancer: A safety net hospital experience.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2025Article
- Review
- A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells.Science signaling · 2024Article
- miR-489 Confines Uncontrolled Estrogen Signaling through a Negative Feedback Mechanism and Regulates Tamoxifen Resistance in Breast Cancer.International journal of molecular sciences · 2022Article
- Ginsenoside Rg1 enhances the healing of injured tendon in achilles tendinitis through the activation of IGF1R signaling mediated by oestrogen receptor.Journal of ginseng research · 2022Article
- Implications of estrogen receptor alpha (ERa) with the intersection of organophosphate flame retardants and diet-induced obesity in adult mice.Journal of toxicology and environmental health. Part A · 2022Article
- The female syndecan-4Frontiers in cell and developmental biology · 2022Article
- Is Estrogen a Missing Culprit in Thyroid Eye Disease? Sex Steroid Hormone Homeostasis Is Key to Other Fibrogenic Autoimmune Diseases - Why Not This One?Frontiers in immunology · 2022Article
- Article
- Differential gene expression in liver of colored broiler chicken divergently selected for residual feed intake.Tropical animal health and production · 2021Article
- Transportin-2 plays a critical role in nucleocytoplasmic shuttling of oestrogen receptor-α.Scientific reports · 2020Article
- Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy.International journal of molecular sciences · 2020Review
- Compensatory Estrogen Signal Is Capable of DNA Repair in Antiestrogen-Responsive Cancer Cells via Activating Mutations.Journal of oncology · 2020Review
- Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway.Journal of ginseng research · 2019Article
- The p52 isoform of SHC1 is a key driver of breast cancer initiation.Breast cancer research : BCR · 2019Article
- Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays.Cellular and molecular life sciences : CMLS · 2019Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Our previous studies demonstrated that 17beta-estradiol (E2) rapidly induces the interaction of estrogen receptor alpha (ERalpha) with the adapter protein Shc, the translocation of ERalpha to the cell membrane, and the formation of dynamic membrane structures in MCF-7 breast cancer cells. The present study examined how E2 causes ERalpha to translocate to the region of the plasma membrane and focused on mechanisms whereby Shc and the insulin-like growth factor-1 receptor (IGF-1R) mediate this process. Shc physically interacts with IGF-1R in the plasma membrane, and E2 activates IGF-1R. We reasoned that ERalpha, when bound to Shc, would be directed to the region of the plasma membrane by the same processes, causing membrane translocation of Shc. We confirmed that E2 rapidly induced IGF-1R phosphorylation and demonstrated that E2 induced formation of a ternary protein complex among Shc, ERalpha, and IGF-1R. Knock down of Shc with a specific small inhibitory RNA decreased the association of ERalpha with IGF-1R by 87%, suggesting that Shc is a crucial molecule in the formation of this ternary complex. Confocal microscopy studies provided further confirmation of the functional roles of Shc and the IGF-1R in the translocation of ERalpha to the region of the membrane. Down-regulation of Shc, ERalpha, or IGF-1R with specific small inhibitory RNAs all blocked E2-induced mitogen-activated protein kinase phosphorylation. Together, our results demonstrate that Shc and IGF-1R serve as key elements in the translocation of ERalpha to the cell membrane and in the facilitation of ERalpha-mediated rapid E2 action.
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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.