The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37
Lymphocyte-specific protein tyrosine kinase (Lck) is a pivotal tyrosine kinase involved in T cell receptor (TCR) signaling. Because of its importance, the activity of Lck is regulated at different levels including phosphorylation of tyrosine residues, protein–protein interactions, and localization....
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/126 |
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| author | Sarah Kowallik Andreas Kritikos Matthias Kästle Christoph Thurm Burkhart Schraven Luca Simeoni |
| author_facet | Sarah Kowallik Andreas Kritikos Matthias Kästle Christoph Thurm Burkhart Schraven Luca Simeoni |
| author_sort | Sarah Kowallik |
| collection | DOAJ |
| description | Lymphocyte-specific protein tyrosine kinase (Lck) is a pivotal tyrosine kinase involved in T cell receptor (TCR) signaling. Because of its importance, the activity of Lck is regulated at different levels including phosphorylation of tyrosine residues, protein–protein interactions, and localization. It has been proposed that the co-chaperone Cdc37, which assists the chaperone heat shock protein 90 (Hsp90) in the folding of client proteins, is also involved in the regulation of the activity/stability of Lck. Nevertheless, the available experimental data do not clearly support this conclusion. Thus, we assessed whether or not Cdc37 regulates Lck. We performed experiments in which the expression of Cdc37 was either augmented or suppressed in Jurkat T cells. The results of our experiments indicated that neither the overexpression nor the suppression of Cdc37 affected Lck stability and activity. Moreover, TCR signaling proceeded normally in T cells in which Cdc37 expression was either augmented or suppressed. Finally, we demonstrated that also under stress conditions Cdc37 was dispensable for the regulation of Lck activity/stability. In conclusion, our data do not support the idea that Lck is a Cdc37 client. |
| first_indexed | 2024-03-10T13:47:22Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:47:22Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-58f6ad4a64be448788a27dd9333e62df2023-11-21T02:29:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122112610.3390/ijms22010126The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37Sarah Kowallik0Andreas Kritikos1Matthias Kästle2Christoph Thurm3Burkhart Schraven4Luca Simeoni5Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, GermanyInstitute of Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, GermanyInstitute of Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, GermanyInstitute of Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, GermanyInstitute of Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, GermanyInstitute of Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, GermanyLymphocyte-specific protein tyrosine kinase (Lck) is a pivotal tyrosine kinase involved in T cell receptor (TCR) signaling. Because of its importance, the activity of Lck is regulated at different levels including phosphorylation of tyrosine residues, protein–protein interactions, and localization. It has been proposed that the co-chaperone Cdc37, which assists the chaperone heat shock protein 90 (Hsp90) in the folding of client proteins, is also involved in the regulation of the activity/stability of Lck. Nevertheless, the available experimental data do not clearly support this conclusion. Thus, we assessed whether or not Cdc37 regulates Lck. We performed experiments in which the expression of Cdc37 was either augmented or suppressed in Jurkat T cells. The results of our experiments indicated that neither the overexpression nor the suppression of Cdc37 affected Lck stability and activity. Moreover, TCR signaling proceeded normally in T cells in which Cdc37 expression was either augmented or suppressed. Finally, we demonstrated that also under stress conditions Cdc37 was dispensable for the regulation of Lck activity/stability. In conclusion, our data do not support the idea that Lck is a Cdc37 client.https://www.mdpi.com/1422-0067/22/1/126Cdc37co-chaperoneLcktyrosine kinaseTCR signalingheat shock protein 90 (Hsp90) |
| spellingShingle | Sarah Kowallik Andreas Kritikos Matthias Kästle Christoph Thurm Burkhart Schraven Luca Simeoni The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37 International Journal of Molecular Sciences Cdc37 co-chaperone Lck tyrosine kinase TCR signaling heat shock protein 90 (Hsp90) |
| title | The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37 |
| title_full | The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37 |
| title_fullStr | The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37 |
| title_full_unstemmed | The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37 |
| title_short | The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37 |
| title_sort | activity and stability of p56lck and tcr signaling do not depend on the co chaperone cdc37 |
| topic | Cdc37 co-chaperone Lck tyrosine kinase TCR signaling heat shock protein 90 (Hsp90) |
| url | https://www.mdpi.com/1422-0067/22/1/126 |
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