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Article

Phosphorylation in the Charged Linker Modulates Interactions and Secretion of Hsp90β

Protein Analysis Facility, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland
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Academic Editor: Alexander E. Kabakov
Cells 2021, 10(7), 1701; https://doi.org/10.3390/cells10071701
Received: 18 May 2021 / Revised: 28 June 2021 / Accepted: 30 June 2021 / Published: 5 July 2021
Hsp90β is a major chaperone involved in numerous cellular processes. Hundreds of client proteins depend on Hsp90β for proper folding and/or activity. Regulation of Hsp90β is critical to coordinate its tasks and is mediated by several post-translational modifications. Here, we focus on two phosphorylation sites located in the charged linker region of human Hsp90β, Ser226 and Ser255, which have been frequently reported but whose function remains unclear. Targeted measurements by mass spectrometry indicated that intracellular Hsp90β is highly phosphorylated on both sites (>90%). The level of phosphorylation was unaffected by various stresses (e.g., heat shock, inhibition with drugs) that impact Hsp90β activity. Mutating the two serines to alanines increased the amount of proteins interacting with Hsp90β globally and increased the sensitivity to tryptic cleavage in the C-terminal domain. Further investigation revealed that phosphorylation on Ser255 and to a lesser extent on Ser226 is decreased in the conditioned medium of cultured K562 cells, and that a non-phosphorylatable double alanine mutant was secreted more efficiently than the wild type. Overall, our results show that phosphorylation events in the charged linker regulate both the interactions of Hsp90β and its secretion, through changes in the conformation of the chaperone. View Full-Text
Keywords: heat shock protein 90; chaperone; charged linker; phosphorylation; interactome; proteomics heat shock protein 90; chaperone; charged linker; phosphorylation; interactome; proteomics
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MDPI and ACS Style

Weidenauer, L.; Quadroni, M. Phosphorylation in the Charged Linker Modulates Interactions and Secretion of Hsp90β. Cells 2021, 10, 1701. https://doi.org/10.3390/cells10071701

AMA Style

Weidenauer L, Quadroni M. Phosphorylation in the Charged Linker Modulates Interactions and Secretion of Hsp90β. Cells. 2021; 10(7):1701. https://doi.org/10.3390/cells10071701

Chicago/Turabian Style

Weidenauer, Lorenz, and Manfredo Quadroni. 2021. "Phosphorylation in the Charged Linker Modulates Interactions and Secretion of Hsp90β" Cells 10, no. 7: 1701. https://doi.org/10.3390/cells10071701

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