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Cited by 416Heat shock proteins researchProtein Kinase Regulation and GTPase SignalingCancer-related Molecular Pathways

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.

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Xu, Y, Lindquist, S·1993·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.90.15.7074PMC PMC47078
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Abstract

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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Research works printed but not linked: 4

  1. [3]Shilo, B. Z. & Weinberg, R. A. (1981) Proc. Natl. Acad. Sci. USA 78, 6789–6792.
  2. [8]Iba, H., Takeya, T., Cross, F. R., Hanafusa, T. & Hanafusa, H. (1984) Proc. Natl. Acad. Sci. USA 81, 4424–4428.
  3. [13]Oppermann, H., Levinson, W. & Bishop, J. M. (1981) Proc. Natl. Acad. Sci. USA 78, 1067–1071.
  4. [24]Kornbluth, S., Jove, R. & Hanafusa, H. (1987) Proc. Natl. Acad. Sci. USA 84, 4455–4459.

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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
DOI
10.1073/pnas.90.15.7074
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
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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