title: Hsp90 chaperone complexes are required for the activity and stability of yeast protein kinases Mik1, Wee1 and Swe1.
abstract: The Wee1 protein kinase negatively regulates entry into mitosis by mediating the inhibitory tyrosine phosphorylation of Cdc2-cyclin B kinase. The stability and activity of Wee1 from the fission yeast Schizosaccharomyces pombe is critically dependent on functional Hsp90 chaperones. Here we identify two related tyrosine protein kinases, Mik1 from fission yeast and its Saccharomyces cerevisiae homolog Swe1, as Hsp90 substrates and show that the kinase domain is sufficient to mediate this interaction. Morphological and biochemical defects arising from overexpression of the kinases in fission yeast are suppressed in the conditional Hsp90 mutant swo1-26. A subset of all three kinases is associated with the Hsp90 cochaperones cyclophilin 40 and p23. Under conditions of impaired chaperone function or treatment with the Hsp90 inhibitory drug geldanamycin, intracellular levels of the kinases are reduced and the proteins become rapidly degraded by the proteasome machinery, indicating that Wee1, Mik1 and Swe1 require Hsp90 heterocomplexes for their stability and maintenance of function.
authors: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
authors: F S
authors: FS
authors: Goes
authors: J
authors: J
authors: Martin
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D016227:Benzoquinones; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000939:Epitopes / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D047029:Lactams, Macrocyclic; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D011809:Quinones / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000737:chemistry; D029702:Schizosaccharomyces pombe Proteins; D013696:Temperature; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000081406:Peptidyl-Prolyl Isomerase F; D004791:Enzyme Inhibitors; D000939:Epitopes; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009687:Nuclear Proteins; D011809:Quinones; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C099685:SWE1 protein, S cerevisiae; C090679:mik1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase; C001277:geldanamycin