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PMID: 14742721 Published · ppublish English Journal Article

Sti1 and Cdc37 can stabilize Hsp90 in chaperone complexes with a protein kinase.

Molecular biology of the cell ·Vol. 15 ·No. 4 ·2004-04-00 ·Pages 1785-92

Lee P, Shabbir A, Cardozo C, Caplan AJ

Abstract

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/chemistry Cell Cycle Proteins/metabolism,physiology Drosophila Proteins/metabolism,physiology Fungal Proteins/physiology Gene Expression Regulation HSP90 Heat-Shock Proteins/metabolism Heat-Shock Proteins Lac Operon MAP Kinase Kinase Kinases/metabolism MAP Kinase Signaling System Models, Biological Molecular Chaperones/metabolism,physiology Mutation Pheromones/metabolism Plasmids/metabolism Protein Binding RNA/chemistry Reverse Transcriptase Polymerase Chain Reaction Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins Signal Transduction Temperature Time Factors
Chemicals
CDC37 protein, S cerevisiae Carrier Proteins Cell Cycle Proteins Drosophila Proteins Fungal Proteins HSP90 Heat-Shock Proteins Heat-Shock Proteins Molecular Chaperones Pheromones STI1 protein, S cerevisiae Saccharomyces cerevisiae Proteins RNA MAP Kinase Kinase Kinases Ste11 protein, S cerevisiae
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lee Paul
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Shabbir Arsalan
Cardozo Christopher
Caplan Avrom J
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e03-07-0480
Published
2004-04-00
Epub
2004-00-23
Pages
1785-92
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC379275
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e03-07-0480 PMC Full Text View journal details
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