ArticleProceedings of the National Academy of Sciences of the United States of America1999
Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90.
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 73 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.
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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
73 citing papers in PubMed, 181 citations in OpenAlex.
- The Hsp90 Molecular Chaperone as a Global Modifier of the Genotype-Phenotype-Fitness Map: An Evolutionary Perspective.Journal of molecular biology · 2024Review
- Molecular determinants of Hsp90 dependence of Src kinase revealed by deep mutational scanning.Protein science : a publication of the Protein Society · 2023Article
- The roles of molecular chaperones in regulating cell metabolism.FEBS letters · 2023Review
- Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities.Oncogene · 2023Review
- Article
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- GroEL/S Overexpression Helps to Purge Deleterious Mutations and Reduce Genetic Diversity during Adaptive Protein Evolution.Molecular biology and evolution · 2022Article
- Heterogeneous Responses and Isoform Compensation the Dim Therapeutic Window of Hsp90 ATP-Binding Inhibitors in Cancer.Molecular and cellular biology · 2022Article
- AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas.Scientific reports · 2021Article
- Article
- Clinical Significance of Monitoring Circulating Free DNA and Plasma Heat Shock Protein 90alpha in Patients with Esophageal Squamous Cell Carcinoma.Cancer management and research · 2021Article
- The Mitochondrial Hsp90 TRAP1 and Alzheimer's Disease.Frontiers in molecular biosciences · 2021Review
- Sildenafil triggers tumor lethality through altered expression of HSP90 and degradation of PKD2.Carcinogenesis · 2020Article
- Folic acid prevents the progesterone-promoted proliferation and migration in breast cancer cell lines.European journal of nutrition · 2020Article
- The Yeast Hsp70 Cochaperone Ydj1 Regulates Functional Distinction of Ssa Hsp70s in the Hsp90 Chaperoning Pathway.Genetics · 2020Article
- Inhibition of HSP90 overcomes melphalan resistance through downregulation of Src in multiple myeloma cells.Clinical and experimental medicine · 2020Article
- Old and New Approaches to Target the Hsp90 Chaperone.Current cancer drug targets · 2020Review
- Review
- Stimulation of heat shock protein 90 chaperone function through binding of a novobiocin analog KU-32.The Journal of biological chemistry · 2019Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Although Hsp90 displays general chaperone activity in vitro, few substrates of the chaperone have been identified in vivo, and the characteristics that render these substrates dependent on Hsp90 remain elusive. To investigate this issue, we exploited a paradoxical observation: several unrelated oncogenic viral tyrosine kinases, including v-src, attain their native conformation after association with Hsp90, yet their nearly identical cellular homologs interact only weakly with the chaperone. It has been controversial whether Hsp90 is vital for normal maturation of the cellular kinases or is simply binding a misfolded subfraction of the proteins. By modulating Hsp90 levels in Saccharomyces cerevisiae, we determined that Hsp90 is indeed necessary for the maturation of c-src (the normal homolog of v-src). c-src maturation is, however, less sensitive to Hsp90 perturbations than is v-src maturation. Dependence of the two proteins on Hsp90 does not correspond to their relative efficiency in reaching their final destination (the plasma membrane); we observed that in yeast, unlike in vertebrate cells, neither c-src nor v-src concentrate in the membrane. Expression of different v/c-src chimeras in cells carrying wild-type or temperature-sensitive Hsp90 alleles revealed that the difference between the proteins instead arises from multiple, naturally occurring mutations in the C-terminal region of v-src.
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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.