Negative regulation of mitosis in fission yeast by the Shk1-interacting protein Skb1 and its human homolog, Skb1Hs
We previously provided evidence that the protein encoded by the highly conserved skb1 gene is a putative regulator of Shk1, a p21(Cdc42/Rac)-activated kinase (PAK) homolog in the fission yeast Schizosaccharomyces pombe. skb1 null mutants are viable and competent for mating but less elongate than wil...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1998-12, Vol.95 (25), p.14781-14786 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Gilbreth, M. (University of Texas, Houston.) Yang, P Bartholomeusz, G Pimental, R.A Kansra, S Gadiraju, R Marcus, S |
| description | We previously provided evidence that the protein encoded by the highly conserved skb1 gene is a putative regulator of Shk1, a p21(Cdc42/Rac)-activated kinase (PAK) homolog in the fission yeast Schizosaccharomyces pombe. skb1 null mutants are viable and competent for mating but less elongate than wild-type S. pombe cells, whereas cells that overexpress sib1 are hyperelongated. These phenotypes suggest a possible role for Skb1 as a mitotic inhibitor. Here we show genetic interactions of both skb1 and shk1 with genes encoding key mitotic regulators in S. pombe. Our results indicate that Skb1 negatively regulates mitosis by a mechanism that is independent of the Cdc2-activating phosphatase Cdc25 but that is at least partially dependent on Shk1 and the Cdc2 inhibitory kinase Wee1. We provide biochemical evidence for association of Skb1 and Shk1 with Cdc2 in S. pombe, suggesting that Skb1 and Shk1 inhibit mitosis through interaction with the Cdc2 complex, rather than by an indirect mechanism. These results provide evidence of a previously undescribed role for PAK-related protein kinases as mitotic inhibitors. We also describe the cloning of a human homolog of skb1, SKB1Hs, and show that it can functionally replace skb1 in S. pombe. Thus, the molecular functions of Skb1-related proteins have likely been substantially conserved through evolution |
| doi_str_mv | 10.1073/pnas.95.25.14781 |
| format | Article |
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(University of Texas, Houston.) ; Yang, P ; Bartholomeusz, G ; Pimental, R.A ; Kansra, S ; Gadiraju, R ; Marcus, S</creator><creatorcontrib>Gilbreth, M. (University of Texas, Houston.) ; Yang, P ; Bartholomeusz, G ; Pimental, R.A ; Kansra, S ; Gadiraju, R ; Marcus, S</creatorcontrib><description>We previously provided evidence that the protein encoded by the highly conserved skb1 gene is a putative regulator of Shk1, a p21(Cdc42/Rac)-activated kinase (PAK) homolog in the fission yeast Schizosaccharomyces pombe. skb1 null mutants are viable and competent for mating but less elongate than wild-type S. pombe cells, whereas cells that overexpress sib1 are hyperelongated. These phenotypes suggest a possible role for Skb1 as a mitotic inhibitor. Here we show genetic interactions of both skb1 and shk1 with genes encoding key mitotic regulators in S. pombe. Our results indicate that Skb1 negatively regulates mitosis by a mechanism that is independent of the Cdc2-activating phosphatase Cdc25 but that is at least partially dependent on Shk1 and the Cdc2 inhibitory kinase Wee1. We provide biochemical evidence for association of Skb1 and Shk1 with Cdc2 in S. pombe, suggesting that Skb1 and Shk1 inhibit mitosis through interaction with the Cdc2 complex, rather than by an indirect mechanism. These results provide evidence of a previously undescribed role for PAK-related protein kinases as mitotic inhibitors. We also describe the cloning of a human homolog of skb1, SKB1Hs, and show that it can functionally replace skb1 in S. pombe. Thus, the molecular functions of Skb1-related proteins have likely been substantially conserved through evolution</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.95.25.14781</identifier><identifier>PMID: 9843966</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; BINDING PROTEINS ; Carrier Proteins - genetics ; Cell division ; Cell growth ; Cells ; Complementary DNA ; ENZYME INHIBITORS ; Enzymes ; Evolution ; Evolutionary genetics ; FENOTIPOS ; GENE ; Gene Expression Regulation, Fungal ; GENE INTERACTION ; GENES ; Genetic mutation ; Genetics ; Government regulation ; HeLa cells ; Humans ; INHIBIDORES DE ENZIMAS ; INHIBITEUR D'ENZYME ; INTERACCION DE GENES ; INTERACTION GENIQUE ; Methyltransferases ; MITOSE ; MITOSIS ; Mitosis - genetics ; Molecular Sequence Data ; MUTANT ; MUTANTES ; MUTANTS ; p21-Activated Kinases ; PHENOTYPE ; PHENOTYPES ; Plasmids ; PROTEIN KINASE ; Protein-Serine-Threonine Kinases - genetics ; PROTEINA QUINASA ; PROTEINAS AGLUTINANTES ; PROTEINE DE LIAISON ; PROTEINE KINASE ; Proteins ; Schizosaccharomyces - cytology ; Schizosaccharomyces - genetics ; SCHIZOSACCHAROMYCES POMBE ; Schizosaccharomyces pombe Proteins ; Sequence Alignment ; Sequence Homology, Amino Acid ; SHK1 GENE ; SKB1 GENE ; Yeast ; Yeasts</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1998-12, Vol.95 (25), p.14781-14786</ispartof><rights>Copyright 1993-1998 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Dec 8, 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/46620$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/46620$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,777,781,800,27905,27906,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9843966$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gilbreth, M. (University of Texas, Houston.)</creatorcontrib><creatorcontrib>Yang, P</creatorcontrib><creatorcontrib>Bartholomeusz, G</creatorcontrib><creatorcontrib>Pimental, R.A</creatorcontrib><creatorcontrib>Kansra, S</creatorcontrib><creatorcontrib>Gadiraju, R</creatorcontrib><creatorcontrib>Marcus, S</creatorcontrib><title>Negative regulation of mitosis in fission yeast by the Shk1-interacting protein Skb1 and its human homolog, Skb1Hs</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We previously provided evidence that the protein encoded by the highly conserved skb1 gene is a putative regulator of Shk1, a p21(Cdc42/Rac)-activated kinase (PAK) homolog in the fission yeast Schizosaccharomyces pombe. skb1 null mutants are viable and competent for mating but less elongate than wild-type S. pombe cells, whereas cells that overexpress sib1 are hyperelongated. These phenotypes suggest a possible role for Skb1 as a mitotic inhibitor. Here we show genetic interactions of both skb1 and shk1 with genes encoding key mitotic regulators in S. pombe. Our results indicate that Skb1 negatively regulates mitosis by a mechanism that is independent of the Cdc2-activating phosphatase Cdc25 but that is at least partially dependent on Shk1 and the Cdc2 inhibitory kinase Wee1. We provide biochemical evidence for association of Skb1 and Shk1 with Cdc2 in S. pombe, suggesting that Skb1 and Shk1 inhibit mitosis through interaction with the Cdc2 complex, rather than by an indirect mechanism. These results provide evidence of a previously undescribed role for PAK-related protein kinases as mitotic inhibitors. We also describe the cloning of a human homolog of skb1, SKB1Hs, and show that it can functionally replace skb1 in S. pombe. Thus, the molecular functions of Skb1-related proteins have likely been substantially conserved through evolution</description><subject>Amino Acid Sequence</subject><subject>BINDING PROTEINS</subject><subject>Carrier Proteins - genetics</subject><subject>Cell division</subject><subject>Cell growth</subject><subject>Cells</subject><subject>Complementary DNA</subject><subject>ENZYME INHIBITORS</subject><subject>Enzymes</subject><subject>Evolution</subject><subject>Evolutionary genetics</subject><subject>FENOTIPOS</subject><subject>GENE</subject><subject>Gene Expression Regulation, Fungal</subject><subject>GENE INTERACTION</subject><subject>GENES</subject><subject>Genetic mutation</subject><subject>Genetics</subject><subject>Government regulation</subject><subject>HeLa cells</subject><subject>Humans</subject><subject>INHIBIDORES DE ENZIMAS</subject><subject>INHIBITEUR D'ENZYME</subject><subject>INTERACCION DE GENES</subject><subject>INTERACTION GENIQUE</subject><subject>Methyltransferases</subject><subject>MITOSE</subject><subject>MITOSIS</subject><subject>Mitosis - genetics</subject><subject>Molecular Sequence Data</subject><subject>MUTANT</subject><subject>MUTANTES</subject><subject>MUTANTS</subject><subject>p21-Activated Kinases</subject><subject>PHENOTYPE</subject><subject>PHENOTYPES</subject><subject>Plasmids</subject><subject>PROTEIN KINASE</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>PROTEINA QUINASA</subject><subject>PROTEINAS AGLUTINANTES</subject><subject>PROTEINE DE LIAISON</subject><subject>PROTEINE KINASE</subject><subject>Proteins</subject><subject>Schizosaccharomyces - cytology</subject><subject>Schizosaccharomyces - genetics</subject><subject>SCHIZOSACCHAROMYCES POMBE</subject><subject>Schizosaccharomyces pombe Proteins</subject><subject>Sequence Alignment</subject><subject>Sequence Homology, Amino Acid</subject><subject>SHK1 GENE</subject><subject>SKB1 GENE</subject><subject>Yeast</subject><subject>Yeasts</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE2LFDEQhoMo67h6F0EIHjzZY1UnnY-jLOoKix7GPTfp7qQns93J2EkL8-_NuoOCF6GginqfeqkqQl4ibBEke38MJm11s62bLXKp8BHZIGisBNfwmGwAalkpXvOn5FlKBwDQjYILcqEVZ1qIDVm-2tFk_9PSxY7rVMoYaHR09jkmn6gP1PmU7rsna1Km3YnmvaW7_R1WPmS7mD77MNLjErMt9O6uQ2rCQH1OdL_OJtB9nOMUx3e_tev0nDxxZkr2xTlfkttPH79fXVc33z5_ufpwUzkGTa663vRKOqFq4WTX1dIYx8WAbHCdGRgAL1iJoSl9JXsclGm4sJoxgciQXZK3D75ltR-rTbmdfertNJlg45paCYhCYvNfECXy8tB7xzf_gIe4LqEc0daArBYKVIFen6G1m-3QHhc_m-XUnl9e9FcP-iHluPyRuRA1_B12JrZmXHxqb3eotQYEITT7BWNklL0</recordid><startdate>19981208</startdate><enddate>19981208</enddate><creator>Gilbreth, M. (University of Texas, Houston.)</creator><creator>Yang, P</creator><creator>Bartholomeusz, G</creator><creator>Pimental, R.A</creator><creator>Kansra, S</creator><creator>Gadiraju, R</creator><creator>Marcus, S</creator><general>National Academy of Sciences of the United States of America</general><general>National Academy of Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19981208</creationdate><title>Negative regulation of mitosis in fission yeast by the Shk1-interacting protein Skb1 and its human homolog, Skb1Hs</title><author>Gilbreth, M. (University of Texas, Houston.) ; Yang, P ; Bartholomeusz, G ; Pimental, R.A ; Kansra, S ; Gadiraju, R ; Marcus, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-f305t-bcac87f6826f7bb27aaf46d13dfbad3004305305d5af487c1d8a546e933611313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Amino Acid Sequence</topic><topic>BINDING PROTEINS</topic><topic>Carrier Proteins - genetics</topic><topic>Cell division</topic><topic>Cell growth</topic><topic>Cells</topic><topic>Complementary DNA</topic><topic>ENZYME INHIBITORS</topic><topic>Enzymes</topic><topic>Evolution</topic><topic>Evolutionary genetics</topic><topic>FENOTIPOS</topic><topic>GENE</topic><topic>Gene Expression Regulation, Fungal</topic><topic>GENE INTERACTION</topic><topic>GENES</topic><topic>Genetic mutation</topic><topic>Genetics</topic><topic>Government regulation</topic><topic>HeLa cells</topic><topic>Humans</topic><topic>INHIBIDORES DE ENZIMAS</topic><topic>INHIBITEUR D'ENZYME</topic><topic>INTERACCION DE GENES</topic><topic>INTERACTION GENIQUE</topic><topic>Methyltransferases</topic><topic>MITOSE</topic><topic>MITOSIS</topic><topic>Mitosis - genetics</topic><topic>Molecular Sequence Data</topic><topic>MUTANT</topic><topic>MUTANTES</topic><topic>MUTANTS</topic><topic>p21-Activated Kinases</topic><topic>PHENOTYPE</topic><topic>PHENOTYPES</topic><topic>Plasmids</topic><topic>PROTEIN KINASE</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>PROTEINA QUINASA</topic><topic>PROTEINAS AGLUTINANTES</topic><topic>PROTEINE DE LIAISON</topic><topic>PROTEINE KINASE</topic><topic>Proteins</topic><topic>Schizosaccharomyces - cytology</topic><topic>Schizosaccharomyces - genetics</topic><topic>SCHIZOSACCHAROMYCES POMBE</topic><topic>Schizosaccharomyces pombe Proteins</topic><topic>Sequence Alignment</topic><topic>Sequence Homology, Amino Acid</topic><topic>SHK1 GENE</topic><topic>SKB1 GENE</topic><topic>Yeast</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gilbreth, M. (University of Texas, Houston.)</creatorcontrib><creatorcontrib>Yang, P</creatorcontrib><creatorcontrib>Bartholomeusz, G</creatorcontrib><creatorcontrib>Pimental, R.A</creatorcontrib><creatorcontrib>Kansra, S</creatorcontrib><creatorcontrib>Gadiraju, R</creatorcontrib><creatorcontrib>Marcus, S</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gilbreth, M. (University of Texas, Houston.)</au><au>Yang, P</au><au>Bartholomeusz, G</au><au>Pimental, R.A</au><au>Kansra, S</au><au>Gadiraju, R</au><au>Marcus, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Negative regulation of mitosis in fission yeast by the Shk1-interacting protein Skb1 and its human homolog, Skb1Hs</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1998-12-08</date><risdate>1998</risdate><volume>95</volume><issue>25</issue><spage>14781</spage><epage>14786</epage><pages>14781-14786</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>We previously provided evidence that the protein encoded by the highly conserved skb1 gene is a putative regulator of Shk1, a p21(Cdc42/Rac)-activated kinase (PAK) homolog in the fission yeast Schizosaccharomyces pombe. skb1 null mutants are viable and competent for mating but less elongate than wild-type S. pombe cells, whereas cells that overexpress sib1 are hyperelongated. These phenotypes suggest a possible role for Skb1 as a mitotic inhibitor. Here we show genetic interactions of both skb1 and shk1 with genes encoding key mitotic regulators in S. pombe. Our results indicate that Skb1 negatively regulates mitosis by a mechanism that is independent of the Cdc2-activating phosphatase Cdc25 but that is at least partially dependent on Shk1 and the Cdc2 inhibitory kinase Wee1. We provide biochemical evidence for association of Skb1 and Shk1 with Cdc2 in S. pombe, suggesting that Skb1 and Shk1 inhibit mitosis through interaction with the Cdc2 complex, rather than by an indirect mechanism. These results provide evidence of a previously undescribed role for PAK-related protein kinases as mitotic inhibitors. We also describe the cloning of a human homolog of skb1, SKB1Hs, and show that it can functionally replace skb1 in S. pombe. Thus, the molecular functions of Skb1-related proteins have likely been substantially conserved through evolution</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>9843966</pmid><doi>10.1073/pnas.95.25.14781</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1998-12, Vol.95 (25), p.14781-14786 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70116715 |
| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence BINDING PROTEINS Carrier Proteins - genetics Cell division Cell growth Cells Complementary DNA ENZYME INHIBITORS Enzymes Evolution Evolutionary genetics FENOTIPOS GENE Gene Expression Regulation, Fungal GENE INTERACTION GENES Genetic mutation Genetics Government regulation HeLa cells Humans INHIBIDORES DE ENZIMAS INHIBITEUR D'ENZYME INTERACCION DE GENES INTERACTION GENIQUE Methyltransferases MITOSE MITOSIS Mitosis - genetics Molecular Sequence Data MUTANT MUTANTES MUTANTS p21-Activated Kinases PHENOTYPE PHENOTYPES Plasmids PROTEIN KINASE Protein-Serine-Threonine Kinases - genetics PROTEINA QUINASA PROTEINAS AGLUTINANTES PROTEINE DE LIAISON PROTEINE KINASE Proteins Schizosaccharomyces - cytology Schizosaccharomyces - genetics SCHIZOSACCHAROMYCES POMBE Schizosaccharomyces pombe Proteins Sequence Alignment Sequence Homology, Amino Acid SHK1 GENE SKB1 GENE Yeast Yeasts |
| title | Negative regulation of mitosis in fission yeast by the Shk1-interacting protein Skb1 and its human homolog, Skb1Hs |
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