Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae.
Ste5 is a Zn2+ finger-like protein thought to function before three kinases, Ste11 (a MEKK), Ste7 (a MEK), and Fus3 (a MAPK), in a conserved MAP kinase cascade required for mating in S. cerevisiae. Here, we present evidence that Ste5 forms a multikinase complex that joins these kinases for efficient ... Fus3 activation. By two-hybrid analysis, Ste11, Ste7, and Fus3 associate with different domains of Ste5, while Kss1, another MAPK, associates with the same domain as Fus3, thus implying that Ste5 simultaneously binds a MEKK, MEK, and MAPK. Ste5 copurifies with Ste11, Fus3, and a hypophosphorylated form of Ste7, and all four proteins cosediment in a glycerol gradient as if in a large complex. Ste5 also increases the amount of Ste11 complexed to Ste7 and Fus3 and is required for Ste11 to function. These results substantiate a novel signal transduction component that physically links multiple kinases within a single cascade.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Base Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, DNA Mutational Analysis, Fungal Proteins, MAP Kinase Kinase Kinases, Macromolecular Substances, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Models, Biological, Molecular Sequence Data, Protein Binding, Protein Kinases, Reproduction, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Schizosaccharomyces pombe Proteins, Signal Transduction, Transcription Factors
Adaptor Proteins, Signal Transducing, Base Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, DNA Mutational Analysis, Fungal Proteins, MAP Kinase Kinase Kinases, Macromolecular Substances, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Models, Biological, Molecular Sequence Data, Protein Binding, Protein Kinases, Reproduction, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Schizosaccharomyces pombe Proteins, Signal Transduction, Transcription Factors
Cell
Date: Aug. 12, 1994
PubMed ID: 8062390
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