Millson, Stefan H., Truman, Andrew W. and Piper, Peter W. (2022) Hsp90 and phosphorylation of the Slt2(Mpk1) MAP kinase activation loop are essential for catalytic, but not non-catalytic, Slt2-mediated transcription in yeast. Cell Stress and Chaperones, 27 (3). pp. 295-304. ISSN 1466-1268
Full content URL: https://doi.org/10.1007/s12192-022-01274-0
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Item Type: | Article |
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Item Status: | Live Archive |
Abstract
In yeast, the Slt2(Mpk1) stress-activated protein kinase directs the activation of two transcription factors, Rlm1 and Swi4/Swi6, in response to cell wall stress. Rlm1 is activated through a phosphorylation by Slt2, whereas the Swi4/Swi6 activation is noncatalytic and triggered by the binding of phosphorylated forms of both Slt2 and a catalytically inactive pseudokinase (Mlp1). Previous studies have delineated a role for the molecular chaperone Hsp90 in the activation of Slt2, but the involvement of Hsp90 in these events of catalytic versus non-catalytic cell integrity signaling has remained elusive. In cells lacking Mlp1, the Hsp90 inhibitor radicicol was found to inhibit the Slt2-mediated catalytic activation of Rlm1, but not the noncatalytic activation of Swi4/Swi6. Mutation of residues in the TEY motif of the Slt2 activation loop strongly impacted both Hsp90 binding and Rlm1-mediated transcription. In contrast, many of these same mutations had only modest effects on Swi4/6 (Slt2-mediated, non-catalytic) transcription, although one that blocked both the Slt2:Hsp90 interaction and Rlm1-mediated transcription (E191G) triggered a hyperactivation of Swi4/6. Taken together, our results cement the importance of the Slt2 activation loop for both the binding of Hsp90 by Slt2 and the catalytic activation of cell integrity signaling.
Keywords: | Hsp90; MAP kinase; Slt2(Mpk1); Transcription activation; Yeast. |
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Subjects: | C Biological Sciences > C760 Biomolecular Science C Biological Sciences > C220 Mycology C Biological Sciences > C440 Molecular Genetics C Biological Sciences > C130 Cell Biology C Biological Sciences > C500 Microbiology |
Divisions: | College of Science > School of Life Sciences |
ID Code: | 49709 |
Deposited On: | 07 Jun 2022 12:43 |
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