ArticleMolecular biology of the cell2000
Hsp90 is essential for the synthesis and subsequent membrane association, but not the maintenance, of the Src-kinase p56(lck).
Article in Molecular biology of the cell, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 89 citations in OpenAlex.
- TBK1 is a signaling hub in coordinating stress-adaptive mechanisms in head and neck cancer progression.Autophagy · 2025Article
- A fluorescence-based sensor for calibrated measurement of protein kinase stability in live cells.Protein science : a publication of the Protein Society · 2024Article
- A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells.bioRxiv : the preprint server for biology · 2023Article
- TRPA1 activation and Hsp90 inhibition synergistically downregulate macrophage activation and inflammatory responses in vitro.BMC immunology · 2023Article
- Hsp90-mediated regulation of DYRK3 couples stress granule disassembly and growth via mTORC1 signaling.EMBO reports · 2021Article
- The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37.International journal of molecular sciences · 2020Article
- The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation.Nature communications · 2020Article
- ATP-Driven Nonequilibrium Activation of Kinase Clients by the Molecular Chaperone Hsp90.Biophysical journal · 2020Article
- How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches.Trends in biochemical sciences · 2017Review
- A new molecular link between defective autophagy and erythroid abnormalities in chorea-acanthocytosis.Blood · 2016Article
- Bipartite Role of Heat Shock Protein 90 (Hsp90) Keeps CRAF Kinase Poised for Activation.The Journal of biological chemistry · 2016Article
- Pharmacoproteomics identifies combinatorial therapy targets for diffuse large B cell lymphoma.The Journal of clinical investigation · 2015Article
- Mechanisms of protein-folding diseases at a glance.Disease models & mechanisms · 2014Review
- Contribution of chaperones to STAT pathway signaling.JAK-STAT · 2014Review
- The anticancer drug AUY922 generates a proteomics fingerprint that is highly conserved among structurally diverse Hsp90 inhibitors.Journal of proteome research · 2013Article
- Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Psychological stress and aging: role of glucocorticoids (GCs).Age (Dordrecht, Netherlands) · 2012Review
- Heat shock protein 90 in plants: molecular mechanisms and roles in stress responses.International journal of molecular sciences · 2012Review
- Proteomics: a strategy to understand the novel targets in protein misfolding and cancer therapy.Expert review of proteomics · 2010Review
- Extracellular Hsp90 serves as a co-factor for MAPK activation and latent viral gene expression during de novo infection by KSHV.Virology · 2010Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinases of the Src family are synthesized as cytosolic proteins that subsequently translocate to membranes. Little is known of the mechanisms responsible for targeting these proteins to membranes, although a role for the cytosolic chaperone Hsp90 has been proposed. Here, we have studied the involvement of Hsp90 in the synthesis, membrane binding, and maintenance of the Src-kinase Lck. Using specific inhibitors of Hsp90, geldanamycin and radicicol, we found that functional Hsp90 is essential for the stability of newly synthesized, but not mature, Lck. Similar results were obtained for two other Src-kinases, c-Src and Lyn. In contrast, LckY505F and LckDeltaSH2, constitutively active Lck mutants lacking the C-terminal regulatory tyrosine or the entire Src homology 2 domain, respectively, required Hsp90 activity to stabilize the mature proteins. Lck synthesized in the absence of Hsp90 activity was degraded within 30-45 min. This unstable Lck was myristoylated normally but did not associate with membranes or CD4, interactions that normally start within minutes of the completion of Lck synthesis. A construct composed of the N-terminal unique domain of Lck fused to green fluorescent protein did not require Hsp90 activity during synthesis. In addition, this protein associated with membranes efficiently in the absence of Hsp90 activity. Together these data suggest that interaction with Hsp90 is necessary for the correct synthesis and subsequent membrane binding of Lck. However, Hsp90 does not appear to play a direct role in Lck membrane, or CD4, association.
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