The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Heat-shock protein hsp90 governs the activity of pp60v-src kinase.
Open accessAbstract
During or immediately after synthesis in vertebrate cells, the oncogenic protein-tyrosine kinase pp60v-src associates with the approximately 90-kDa heat-shock protein (hsp90). In this complex, pp60v-src is not functional as a kinase. When pp60v-src is subsequently found inserted into the plasma membrane, it is active as a kinase and is no longer associated with hsp90. We have taken advantage of genetic manipulations possible in Saccharomyces cerevisiae to investigate the function and specificity of the association between hsp90 and pp60v-src. Expression of pp60v-src is known to be toxic to S. cerevisiae cells. We find that this toxicity is due to a very specific effect on growth, arrest at a particular point in the cell cycle. In cells expressing v-src, a mutation that lowers the level of hsp90 expression (i) relieves cell cycle arrest and rescues growth, (ii) reduces the level of tyrosine phosphorylation mediated by pp60v-src, (iii) changes the pattern of tyrosine phosphorylation, and (iv) reduces the concentration of pp60v-src. We conclude that hsp90 does not simply suppress pp60v-src kinase activity during transit to the plasma membrane, as previously suggested, but also stabilizes the protein and affects both its activity and specificity. This function of hsp90 is highly selective for pp60v-src: the same hsp90 mutation has no effect on the activity or specificity of the exogenous pp160v-abl tyrosine kinase; similarly, it does not affect the specificity and has only a very small effect on the activity of the exogenous pp60c-src kinase.
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“This role as a potentiator for genetic variation has been observed in fungi as well as mammalian cancer cells20,88,135,136.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [136]
In the citing paper
“Second, Hsp90 can enable the phenotypic effects of new mutations either by stabilizing mutant regulators or by stabilizing non-mutant regulators that mediate signalling required for adaptation.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [136]
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Cites
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Items 401–416 of 416
Bobadilla, N. A., & Barrera‐Chimal, J. (2011) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.11652960.12720059
Gracia, B., Montes, P., Gutierrez‐Barrera, A. M., Arun, B., & Karras, G. I. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.14.557795
“Chaperones, especially HSP90, can also modify the effects of disease-associated mutations 18,75-78 .”
BackgroundHuo, Y., Karnawat, R., Liu, L., Knieß, R. A., Gross, M., Chen, X., & Mayer, M. P. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.25.600625
“In addition, we assessed the activity of the oncogenic tyrosine kinase v-Src that inhibits yeast growth when overexpressed and activated by Hsp90 [40].”
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“They also are observed in signal-transduction pathways involving both serinelthreonine kinases (46, 257, 28 1) and tyrosine-specific kinases, including the protooncogene Src (155, 295).”
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“61 In contrast, the proteins impacted after heat shock may only require Cdc37 under conditions that lead to protein misfolding.”
La protéine HSP90 : expression et ciblage dans les hémopathies malignes
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Regulation of estrogen receptor function by molecular chaperones
Beliakoff, J. (2003) · UA Campus Repository (The University of Arizona)
The unfolded protein response and HLA-B27 misfolding : implications for ankylosing spondylitis.
Lemin, A. J. (2010) · Durham e-Theses (Durham University)
Regulation of the Apoptosome in Cancer
Kim, J. (2012)
Metadata
- Authors
- Xu, Y., & Lindquist, S.
- Affiliations
- University of Chicago (US)
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1993-08
- Volume
- 90
- Issue
- 15
- Pages
- 7074-7078
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC47078
- OpenAlex
- W2085643470
- Cited by
- 416
- References
- 33
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 10 · 2015: 5 · 2014: 14 · 2013: 5 · 2012: 12
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Chicago
- National Institutes of Health
- National Institute of General Medical Sciences (GM-25874)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- HSP90, pp60v-src, tyrosine kinase, kinase activation, protein stability, cell cycle arrest, tyrosine phosphorylation, oncogenic kinase, Src kinase, Saccharomyces cerevisiae, kinase specificity
- MeSH terms
- Cell Cycle, Chromosome Deletion, Genes, Fungal, Heat-Shock Proteins, Phosphoproteins, Recombinant Proteins, Saccharomyces cerevisiae, Tyrosine, Oncogene Protein pp60(v-src), Gene Expression, Mutagenesis, Insertional, Oncogene Proteins v-abl, Proto-Oncogene Proteins pp60(c-src), Phosphotyrosine
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