The Src/Csk regulatory circuit arose early in metazoan evolution
We have identified a gene encoding a member of the Csk family of non-receptor protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ hybridization analysis of the distribution of RNA from the Hydra Csk gene indicates that it is expressed in most of the epithelial cells of the...
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description | We have identified a gene encoding a member of the Csk family of non-receptor protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ hybridization analysis of the distribution of RNA from the Hydra Csk gene indicates that it is expressed in most of the epithelial cells of the adult polyp and in gametogenic cells. Comparison of the expression pattern of Hydra Csk with that of STK, the Hydra Src gene orthologue, reveals that the two genes are largely co-expressed. Such co-expression is consistent with a role for Hydra Csk in regulation of STK activity. This possibility was tested directly by coexpressing Hydra Csk with STK in yeast. Co-expression suppressed the growth inhibition seen when STK alone is expressed in yeast. Suppression was dependent on the presence of the putative regulatory tyrosine in the carboxyl-terminal tail of STK. Phosphotyrosine immunoblot analysis confirmed that expression of Csk resulted in suppression of STK kinase activity. Taken together these data indicate that the regulatory circuit involving Src and Csk PTKs was established prior to the divergence of the phylum Cnidaria from the rest of the metazoans. |
doi_str_mv | 10.1038/sj.onc.1203714 |
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A ; MALIK, I. A ; SHENK, M. A ; STEELE, R. E</creator><creatorcontrib>MILLER, M. A ; MALIK, I. A ; SHENK, M. A ; STEELE, R. E</creatorcontrib><description>We have identified a gene encoding a member of the Csk family of non-receptor protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ hybridization analysis of the distribution of RNA from the Hydra Csk gene indicates that it is expressed in most of the epithelial cells of the adult polyp and in gametogenic cells. Comparison of the expression pattern of Hydra Csk with that of STK, the Hydra Src gene orthologue, reveals that the two genes are largely co-expressed. Such co-expression is consistent with a role for Hydra Csk in regulation of STK activity. This possibility was tested directly by coexpressing Hydra Csk with STK in yeast. Co-expression suppressed the growth inhibition seen when STK alone is expressed in yeast. Suppression was dependent on the presence of the putative regulatory tyrosine in the carboxyl-terminal tail of STK. Phosphotyrosine immunoblot analysis confirmed that expression of Csk resulted in suppression of STK kinase activity. Taken together these data indicate that the regulatory circuit involving Src and Csk PTKs was established prior to the divergence of the phylum Cnidaria from the rest of the metazoans.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1203714</identifier><identifier>PMID: 10951585</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Amino acids ; Animals ; Biological and medical sciences ; Biological Evolution ; Catalytic Domain ; Cell Division - genetics ; Cell physiology ; Cnidaria ; Csk protein ; Divergence ; Epithelial cells ; Evolution ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation ; Genes ; Hybridization analysis ; Hydra ; Hydra - physiology ; Invertebrates ; Kinases ; Molecular and cellular biology ; Phosphorylation ; Phosphotyrosine ; Phylogenetics ; Phylogeny ; Polymerase Chain Reaction ; Polyps (organisms) ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Proteins ; Receptor Protein-Tyrosine Kinases - genetics ; Receptor Protein-Tyrosine Kinases - metabolism ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - metabolism ; Regulation ; Responses to growth factors, tumor promotors, other factors ; Src protein ; src-Family Kinases - genetics ; src-Family Kinases - metabolism ; STK gene ; Tyrosine ; Vertebrates ; Yeasts - genetics ; Yeasts - growth & development</subject><ispartof>Oncogene, 2000-08, Vol.19 (34), p.3925-3930</ispartof><rights>2000 INIST-CNRS</rights><rights>COPYRIGHT 2000 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 10, 2000</rights><rights>Macmillan Publishers Limited 2000.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-ada52da5d0397d4679970d4c230d11346f50c849cedc496565177467c8adaa4d3</citedby><cites>FETCH-LOGICAL-c513t-ada52da5d0397d4679970d4c230d11346f50c849cedc496565177467c8adaa4d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1475483$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10951585$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MILLER, M. A</creatorcontrib><creatorcontrib>MALIK, I. A</creatorcontrib><creatorcontrib>SHENK, M. A</creatorcontrib><creatorcontrib>STEELE, R. E</creatorcontrib><title>The Src/Csk regulatory circuit arose early in metazoan evolution</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>We have identified a gene encoding a member of the Csk family of non-receptor protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ hybridization analysis of the distribution of RNA from the Hydra Csk gene indicates that it is expressed in most of the epithelial cells of the adult polyp and in gametogenic cells. Comparison of the expression pattern of Hydra Csk with that of STK, the Hydra Src gene orthologue, reveals that the two genes are largely co-expressed. Such co-expression is consistent with a role for Hydra Csk in regulation of STK activity. This possibility was tested directly by coexpressing Hydra Csk with STK in yeast. Co-expression suppressed the growth inhibition seen when STK alone is expressed in yeast. Suppression was dependent on the presence of the putative regulatory tyrosine in the carboxyl-terminal tail of STK. Phosphotyrosine immunoblot analysis confirmed that expression of Csk resulted in suppression of STK kinase activity. Taken together these data indicate that the regulatory circuit involving Src and Csk PTKs was established prior to the divergence of the phylum Cnidaria from the rest of the metazoans.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Evolution</subject><subject>Catalytic Domain</subject><subject>Cell Division - genetics</subject><subject>Cell physiology</subject><subject>Cnidaria</subject><subject>Csk protein</subject><subject>Divergence</subject><subject>Epithelial cells</subject><subject>Evolution</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Hybridization analysis</subject><subject>Hydra</subject><subject>Hydra - physiology</subject><subject>Invertebrates</subject><subject>Kinases</subject><subject>Molecular and cellular biology</subject><subject>Phosphorylation</subject><subject>Phosphotyrosine</subject><subject>Phylogenetics</subject><subject>Phylogeny</subject><subject>Polymerase Chain Reaction</subject><subject>Polyps (organisms)</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proteins</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Regulation</subject><subject>Responses to growth factors, tumor promotors, other factors</subject><subject>Src protein</subject><subject>src-Family Kinases - genetics</subject><subject>src-Family Kinases - metabolism</subject><subject>STK gene</subject><subject>Tyrosine</subject><subject>Vertebrates</subject><subject>Yeasts - genetics</subject><subject>Yeasts - growth & development</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkV1rFDEUhoModl299VIGFe9me_I1mdxZFr-g4IX1OsQkU7POJDWZEdZf72m7aCktEkIged5zkjyEPKewocD747rb5OQ2lAFXVDwgKypU10qpxUOyAi2h1YyzI_Kk1h0AKA3sMTmieEJlL1fk7dn30Hwp7nhbfzQlnC-jnXPZNy4Wt8S5sSXX0ARbxn0TUzOF2f7ONjXhVx6XOeb0lDwa7FjDs8O6Jl_fvzvbfmxPP3_4tD05bZ2kfG6tt5Lh9MC18qJTWivwwjEOnlIuukGC64V2wTuhO9lJqhRirsekFZ6vyZvruhcl_1xCnc0UqwvjaFPISzWKKgyp7r_gFSfxV9bk1S1wl5eS8BGGdYJyyhjvkXp5L8UUB87Qw99S53YMJqYhz8W6y77mhAEIyRFDanMHhcOHKbqcwhBx_66AQwu1hMFclDjZsjcUzKV-U3cG9ZuDfgy8OFx2-TYFfwO_9o3A6wNgq7PjUGxysf7jhJKi5_wPWhKz-w</recordid><startdate>20000810</startdate><enddate>20000810</enddate><creator>MILLER, M. 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Psychology</topic><topic>Gene Expression Regulation</topic><topic>Genes</topic><topic>Hybridization analysis</topic><topic>Hydra</topic><topic>Hydra - physiology</topic><topic>Invertebrates</topic><topic>Kinases</topic><topic>Molecular and cellular biology</topic><topic>Phosphorylation</topic><topic>Phosphotyrosine</topic><topic>Phylogenetics</topic><topic>Phylogeny</topic><topic>Polymerase Chain Reaction</topic><topic>Polyps (organisms)</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proteins</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Regulation</topic><topic>Responses to growth factors, tumor promotors, other factors</topic><topic>Src protein</topic><topic>src-Family Kinases - genetics</topic><topic>src-Family Kinases - metabolism</topic><topic>STK gene</topic><topic>Tyrosine</topic><topic>Vertebrates</topic><topic>Yeasts - genetics</topic><topic>Yeasts - growth & development</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MILLER, M. 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A</au><au>MALIK, I. A</au><au>SHENK, M. A</au><au>STEELE, R. E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Src/Csk regulatory circuit arose early in metazoan evolution</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2000-08-10</date><risdate>2000</risdate><volume>19</volume><issue>34</issue><spage>3925</spage><epage>3930</epage><pages>3925-3930</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>We have identified a gene encoding a member of the Csk family of non-receptor protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ hybridization analysis of the distribution of RNA from the Hydra Csk gene indicates that it is expressed in most of the epithelial cells of the adult polyp and in gametogenic cells. Comparison of the expression pattern of Hydra Csk with that of STK, the Hydra Src gene orthologue, reveals that the two genes are largely co-expressed. Such co-expression is consistent with a role for Hydra Csk in regulation of STK activity. This possibility was tested directly by coexpressing Hydra Csk with STK in yeast. Co-expression suppressed the growth inhibition seen when STK alone is expressed in yeast. Suppression was dependent on the presence of the putative regulatory tyrosine in the carboxyl-terminal tail of STK. Phosphotyrosine immunoblot analysis confirmed that expression of Csk resulted in suppression of STK kinase activity. Taken together these data indicate that the regulatory circuit involving Src and Csk PTKs was established prior to the divergence of the phylum Cnidaria from the rest of the metazoans.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>10951585</pmid><doi>10.1038/sj.onc.1203714</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino acids Animals Biological and medical sciences Biological Evolution Catalytic Domain Cell Division - genetics Cell physiology Cnidaria Csk protein Divergence Epithelial cells Evolution Fundamental and applied biological sciences. Psychology Gene Expression Regulation Genes Hybridization analysis Hydra Hydra - physiology Invertebrates Kinases Molecular and cellular biology Phosphorylation Phosphotyrosine Phylogenetics Phylogeny Polymerase Chain Reaction Polyps (organisms) Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Proteins Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism Regulation Responses to growth factors, tumor promotors, other factors Src protein src-Family Kinases - genetics src-Family Kinases - metabolism STK gene Tyrosine Vertebrates Yeasts - genetics Yeasts - growth & development |
title | The Src/Csk regulatory circuit arose early in metazoan evolution |
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