ArticleProceedings of the National Academy of Sciences of the United States of America1999
The HER-2/neu receptor tyrosine kinase gene encodes a secreted autoinhibitor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 128 citations in OpenAlex.
- Soluble isoforms of EGFR family in breast cancer: Advances and clinical relevance (Review).Oncology letters · 2026Review
- Towards resolution of the intron retention paradox in breast cancer.Breast cancer research : BCR · 2022Article
- Identification of personalized neoantigen-based vaccines and immune subtype characteristic analysis of glioblastoma based on abnormal alternative splicing.American journal of cancer research · 2022Article
- Intron-Encoded Domain of Herstatin, An Autoinhibitor of Human Epidermal Growth Factor Receptors, Is Intrinsically Disordered.Frontiers in molecular biosciences · 2022Article
- The Mammalian Ecdysoneless Protein Interacts with RNA Helicase DDX39A To Regulate Nuclear mRNA Export.Molecular and cellular biology · 2021Article
- HER2 splice variants in breast cancer: investigating their impact on diagnosis and treatment outcomes.Oncotarget · 2020Review
- Review
- Association of Her-2 Expression and Clinicopathological Parameters in Colorectal Carcinoma in Indian Population.Open access Macedonian journal of medical sciences · 2019Article
- Studies on the Dual Activity of EGFR and HER-2 Inhibitors Using Structure-Based Drug Design Techniques.International journal of molecular sciences · 2018Article
- Intron retention in viruses and cellular genes: Detention, border controls and passports.Wiley interdisciplinary reviews. RNA · 2018Review
- How is Herstatin, a tumor suppressor splice variant of the oncogene HER2, regulated?RNA biology · 2017Article
- Alternative splicing and cell survival: from tissue homeostasis to disease.Cell death and differentiation · 2016Review
- Evolutionary conservation of a molecular machinery for export and expression of mRNAs with retained introns.RNA (New York, N.Y.) · 2015Article
- Targeted immune therapy of ovarian cancer.Cancer metastasis reviews · 2015Review
- Article
- The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.Journal of mammary gland biology and neoplasia · 2014Review
- Review
- Suppression of heregulin β signaling by the single N-glycan deletion mutant of soluble ErbB3 protein.The Journal of biological chemistry · 2013Article
- A dominant-negative N-terminal fragment of HER2 frequently expressed in breast cancers.Oncogene · 2013Article
- Soluble Human Epidermal Growth Factor Receptor 2 (sHER2) as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma.Diagnostics (Basel, Switzerland) · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER-2/neu (erbB-2) encodes an 185-kDa orphan receptor tyrosine kinase that is constitutively active as a dimer and displays potent oncogenic activity when overexpressed. Here we describe a secreted protein of approximately 68 kDa, designated herstatin, as the product of an alternative HER-2 transcript that retains intron 8. This alternative transcript specifies 340 residues identical to subdomains I and II from the extracellular domain of p185HER-2 followed by a unique C-terminal sequence of 79 aa encoded by intron 8. The recombinant product of the alternative transcript specifically binds to HER-2-transfected cells with a K(D) of approximately 14 nM and was chemically crosslinked to p185HER-2, whereas the intron encoded sequence alone also binds with high affinity to transfected cells and associates with p185 solubilized from cell extracts. The herstatin mRNA is expressed in normal human fetal kidney and liver, but is at reduced levels relative to p185HER-2 mRNA in carcinoma cells that contain an amplified HER-2 gene. Herstatin appears to be an inhibitor of p185HER-2, because it disrupts dimers, reduces tyrosine phosphorylation of p185, and inhibits the anchorage-independent growth of transformed cells that overexpress HER-2.
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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.