Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway
Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2006-02, Vol.311 (5762), p.822-826 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Bhattacharyya, Roby P Remenyi, Attila Good, Matthew C Bashor, Caleb J Falick, Arnold M Lim, Wendell A |
| description | Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active--it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties. |
| doi_str_mv | 10.1126/science.1120941 |
| format | Article |
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We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active--it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1120941</identifier><identifier>PMID: 16424299</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Adaptor Proteins, Signal Transducing - chemistry ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Alleles ; Allosteric Regulation ; Amino Acid Motifs ; Amino acids ; autophosphorylation ; Binding Sites ; Biological and medical sciences ; Crystallography, X-Ray ; Cytometry ; Down-Regulation ; Drug interactions ; Enzyme Activation ; Enzymes ; Fundamental and applied biological sciences. 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We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active--it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.</description><subject>Adaptor Proteins, Signal Transducing - chemistry</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Alleles</subject><subject>Allosteric Regulation</subject><subject>Amino Acid Motifs</subject><subject>Amino acids</subject><subject>autophosphorylation</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Crystallography, X-Ray</subject><subject>Cytometry</subject><subject>Down-Regulation</subject><subject>Drug interactions</subject><subject>Enzyme Activation</subject><subject>Enzymes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gene expression</subject><subject>Growth, nutrition, metabolism, transports, enzymes. 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Psychology</topic><topic>gene expression</topic><topic>Growth, nutrition, metabolism, transports, enzymes. Molecular biology</topic><topic>MAP Kinase Signaling System</topic><topic>Microbiology</topic><topic>mitogen-activated protein kinase</topic><topic>Mitogen-Activated Protein Kinases - chemistry</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Models, Biological</topic><topic>Models, Molecular</topic><topic>Mutation</topic><topic>Mycology</topic><topic>Pheromones</topic><topic>Pheromones - physiology</topic><topic>Phosphorylation</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>protein phosphorylation</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>protein-protein interactions</topic><topic>Proteins</topic><topic>Research Article</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - chemistry</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><topic>Saccharomyces cerevisiae Proteins - 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Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bhattacharyya, Roby P</au><au>Remenyi, Attila</au><au>Good, Matthew C</au><au>Bashor, Caleb J</au><au>Falick, Arnold M</au><au>Lim, Wendell A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2006-02-10</date><risdate>2006</risdate><volume>311</volume><issue>5762</issue><spage>822</spage><epage>826</epage><pages>822-826</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active--it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>16424299</pmid><doi>10.1126/science.1120941</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Science (American Association for the Advancement of Science), 2006-02, Vol.311 (5762), p.822-826 |
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| subjects | Adaptor Proteins, Signal Transducing - chemistry Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Alleles Allosteric Regulation Amino Acid Motifs Amino acids autophosphorylation Binding Sites Biological and medical sciences Crystallography, X-Ray Cytometry Down-Regulation Drug interactions Enzyme Activation Enzymes Fundamental and applied biological sciences. Psychology gene expression Growth, nutrition, metabolism, transports, enzymes. Molecular biology MAP Kinase Signaling System Microbiology mitogen-activated protein kinase Mitogen-Activated Protein Kinases - chemistry Mitogen-Activated Protein Kinases - metabolism Models, Biological Models, Molecular Mutation Mycology Pheromones Pheromones - physiology Phosphorylation Protein Binding Protein Conformation protein phosphorylation Protein Structure, Secondary Protein Structure, Tertiary protein-protein interactions Proteins Research Article Saccharomyces cerevisiae Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - chemistry Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Scaffolds sexual reproduction Signal transduction transcription (genetics) Transcription, Genetic Yeast Yeasts |
| title | Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway |
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