Sti1 and Cdc37 can stabilize Hsp90 in chaperone complexes with a protein kinase.
Hsp90 functions in association with several cochaperones for folding of protein kinases and transcription factors, although the relative contribution of each to the overall reaction is unknown. We assayed the role of nine different cochaperones in the activation of Ste11, a Saccharomyces cerevisiae mitogen-activated protein kinase kinase kinase. Studies on ... signaling via this protein kinase pathway was measured by alpha-factor-stimulated induction of FIG1 or lacZ, and repression of HHF1. Several cochaperone mutants tested had reduced FIG1 induction or HHF1 repression, although to differing extents. The greatest defects were in cpr7Delta, sse1Delta, and ydj1Delta mutants. Assays of Ste11 kinase activity revealed a pattern of defects in the cochaperone mutant strains that were similar to the gene expression studies. Overexpression of CDC37, a chaperone required for protein kinase folding, suppressed defects the sti1Delta mutant back to wild-type levels. CDC37 overexpression also restored stable Hsp90 binding to the Ste11 protein kinase domain in the sti1Delta mutant strain. These data suggest that Cdc37 and Sti1 have functional overlap in stabilizing Hsp90:client complexes. Finally, we show that Cns1 functions in MAP kinase signaling in association with Cpr7.
Mesh Terms:
Blotting, Western, Carrier Proteins, Cell Cycle Proteins, Drosophila Proteins, Fungal Proteins, Gene Expression Regulation, HSP90 Heat-Shock Proteins, Heat-Shock Proteins, Lac Operon, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Models, Biological, Molecular Chaperones, Mutation, Pheromones, Plasmids, Protein Binding, RNA, Reverse Transcriptase Polymerase Chain Reaction, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Temperature, Time Factors
Blotting, Western, Carrier Proteins, Cell Cycle Proteins, Drosophila Proteins, Fungal Proteins, Gene Expression Regulation, HSP90 Heat-Shock Proteins, Heat-Shock Proteins, Lac Operon, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Models, Biological, Molecular Chaperones, Mutation, Pheromones, Plasmids, Protein Binding, RNA, Reverse Transcriptase Polymerase Chain Reaction, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Temperature, Time Factors
Mol. Biol. Cell
Date: Apr. 01, 2004
PubMed ID: 14742721
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