Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1

The signalling cascade including Raf, mitogen-activated protein kinase (MAPK) kinase and extracellular-signal-regulated kinase (ERK) is important in many facets of cellular regulation. Raf is activated through both Ras-dependent and Ras-independent mechanisms, but the regulatory mechanisms of Raf ac...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature cell biology 2003-05, Vol.5 (5), p.427-432
Hauptverfasser: Yoshimura, Akihiko, Sasaki, Atsuo, Taketomi, Takaharu, Kato, Reiko, Saeki, Kazuko, Nonami, Atsushi, Sasaki, Mika, Kuriyama, Masamitsu, Saito, Naoaki, Shibuya, Masabumi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 432
container_issue 5
container_start_page 427
container_title Nature cell biology
container_volume 5
creator Yoshimura, Akihiko
Sasaki, Atsuo
Taketomi, Takaharu
Kato, Reiko
Saeki, Kazuko
Nonami, Atsushi
Sasaki, Mika
Kuriyama, Masamitsu
Saito, Naoaki
Shibuya, Masabumi
description The signalling cascade including Raf, mitogen-activated protein kinase (MAPK) kinase and extracellular-signal-regulated kinase (ERK) is important in many facets of cellular regulation. Raf is activated through both Ras-dependent and Ras-independent mechanisms, but the regulatory mechanisms of Raf activation remain unclear. Two families of membrane-bound molecules, Sprouty and Sprouty-related EVH1-domain-containing protein (Spred) have been identified and characterized as negative regulators of growth-factor-induced ERK activation. But the molecular functions of mammalian Sproutys have not been clarified. Here we show that mammalian Sprouty4 suppresses vascular epithelial growth factor (VEGF)-induced, Ras-independent activation of Raf1 but does not affect epidermal growth factor (EGF)-induced, Ras-dependent activation of Raf1. Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4. In addition, Sprouty4 mutants of the amino-terminal region containing the conserved tyrosine residue, which is necessary for suppressing fibroblast growth factor signalling, still inhibit the VEGF-induced ERK pathway. Our results show that receptor tyrosine kinases use distinct pathways for Raf and ERK activation and that Sprouty4 differentially regulates these pathways.
doi_str_mv 10.1038/ncb978
format Article
fullrecord <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_73235219</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A183287873</galeid><sourcerecordid>A183287873</sourcerecordid><originalsourceid>FETCH-LOGICAL-c456t-737ed01a56b955ccc137f2e9877cdeb7a983617e1211dc1c159a3fb051cda2893</originalsourceid><addsrcrecordid>eNptke1r1TAUxoMo7kX9C0SKguKHzp68NO3HMaYOJ4M7_RzS9PSS0aZdkor3v18uLY6rJpCEPL_zcA4PIa-gOIOCVZ-caWpZPSHHwGWZ81LWT_fvUuSS1fSInIRwVxTAeSGfkyOgEiTn7JjcfNfDoHurXXY7-XGOO56FeZo8hoAh2-iQW9fihOlwMbvcfMu0ifaXjnZ0WbPLmiRbt83imOAOXpBnne4DvlzvU_Lz8-WPi6_59c2Xq4vz69xwUcbUlMS2AC3KphbCGANMdhTrSkrTYiN1XbESJAIFaA0YELVmXVMIMK2mVc1OyfvFNzV9P2OIarDBYN9rh-MclGSUCQp78O1f4N04e5d6UzStSlDKE_Rugba6R2VdN0avzd5RnUPFaCUryRJ19h8q7RYHa0aHnU3_BwUfDwoSE_F33Oo5BHV1uzlk14GMH0Pw2KnJ20H7nYJC7SNWS8QJfLMONDcDto_YmmkCPixASJLbon-c-B-r1wvpdJw9_rFa5Qfyo7TI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222285224</pqid></control><display><type>article</type><title>Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1</title><source>MEDLINE</source><source>Nature</source><source>Alma/SFX Local Collection</source><creator>Yoshimura, Akihiko ; Sasaki, Atsuo ; Taketomi, Takaharu ; Kato, Reiko ; Saeki, Kazuko ; Nonami, Atsushi ; Sasaki, Mika ; Kuriyama, Masamitsu ; Saito, Naoaki ; Shibuya, Masabumi</creator><creatorcontrib>Yoshimura, Akihiko ; Sasaki, Atsuo ; Taketomi, Takaharu ; Kato, Reiko ; Saeki, Kazuko ; Nonami, Atsushi ; Sasaki, Mika ; Kuriyama, Masamitsu ; Saito, Naoaki ; Shibuya, Masabumi</creatorcontrib><description>The signalling cascade including Raf, mitogen-activated protein kinase (MAPK) kinase and extracellular-signal-regulated kinase (ERK) is important in many facets of cellular regulation. Raf is activated through both Ras-dependent and Ras-independent mechanisms, but the regulatory mechanisms of Raf activation remain unclear. Two families of membrane-bound molecules, Sprouty and Sprouty-related EVH1-domain-containing protein (Spred) have been identified and characterized as negative regulators of growth-factor-induced ERK activation. But the molecular functions of mammalian Sproutys have not been clarified. Here we show that mammalian Sprouty4 suppresses vascular epithelial growth factor (VEGF)-induced, Ras-independent activation of Raf1 but does not affect epidermal growth factor (EGF)-induced, Ras-dependent activation of Raf1. Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4. In addition, Sprouty4 mutants of the amino-terminal region containing the conserved tyrosine residue, which is necessary for suppressing fibroblast growth factor signalling, still inhibit the VEGF-induced ERK pathway. Our results show that receptor tyrosine kinases use distinct pathways for Raf and ERK activation and that Sprouty4 differentially regulates these pathways.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb978</identifier><identifier>PMID: 12717443</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Binding sites ; Biomedical and Life Sciences ; Cancer Research ; Cell Biology ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Developmental Biology ; Endothelial Growth Factors - metabolism ; Endothelial Growth Factors - pharmacology ; Epidermal growth factor ; Epidermal Growth Factor - metabolism ; Epidermal Growth Factor - pharmacology ; Eukaryotic Cells - cytology ; Eukaryotic Cells - drug effects ; Eukaryotic Cells - metabolism ; Fibroblast Growth Factors - metabolism ; Fibroblast Growth Factors - pharmacology ; Fibroblasts ; Growth Substances - metabolism ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins - metabolism ; Intercellular Signaling Peptides and Proteins - pharmacology ; Intracellular Signaling Peptides and Proteins ; Kinases ; letter ; Life Sciences ; Lymphokines - metabolism ; Lymphokines - pharmacology ; Mammals ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - genetics ; Mitogen-Activated Protein Kinases - genetics ; Mitogen-Activated Protein Kinases - metabolism ; Mutation - genetics ; Nerve Tissue Proteins - metabolism ; Phosphorylation ; Physiological aspects ; Protein Binding - drug effects ; Protein Binding - genetics ; Protein kinases ; Protein Structure, Tertiary - drug effects ; Protein Structure, Tertiary - genetics ; Proteins ; Proto-Oncogene Proteins c-raf - genetics ; Proto-Oncogene Proteins c-raf - metabolism ; ras Proteins - genetics ; ras Proteins - metabolism ; Receptor Protein-Tyrosine Kinases - drug effects ; Receptor Protein-Tyrosine Kinases - metabolism ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Stem Cells ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors</subject><ispartof>Nature cell biology, 2003-05, Vol.5 (5), p.427-432</ispartof><rights>Springer Nature Limited 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-737ed01a56b955ccc137f2e9877cdeb7a983617e1211dc1c159a3fb051cda2893</citedby><cites>FETCH-LOGICAL-c456t-737ed01a56b955ccc137f2e9877cdeb7a983617e1211dc1c159a3fb051cda2893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12717443$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoshimura, Akihiko</creatorcontrib><creatorcontrib>Sasaki, Atsuo</creatorcontrib><creatorcontrib>Taketomi, Takaharu</creatorcontrib><creatorcontrib>Kato, Reiko</creatorcontrib><creatorcontrib>Saeki, Kazuko</creatorcontrib><creatorcontrib>Nonami, Atsushi</creatorcontrib><creatorcontrib>Sasaki, Mika</creatorcontrib><creatorcontrib>Kuriyama, Masamitsu</creatorcontrib><creatorcontrib>Saito, Naoaki</creatorcontrib><creatorcontrib>Shibuya, Masabumi</creatorcontrib><title>Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>The signalling cascade including Raf, mitogen-activated protein kinase (MAPK) kinase and extracellular-signal-regulated kinase (ERK) is important in many facets of cellular regulation. Raf is activated through both Ras-dependent and Ras-independent mechanisms, but the regulatory mechanisms of Raf activation remain unclear. Two families of membrane-bound molecules, Sprouty and Sprouty-related EVH1-domain-containing protein (Spred) have been identified and characterized as negative regulators of growth-factor-induced ERK activation. But the molecular functions of mammalian Sproutys have not been clarified. Here we show that mammalian Sprouty4 suppresses vascular epithelial growth factor (VEGF)-induced, Ras-independent activation of Raf1 but does not affect epidermal growth factor (EGF)-induced, Ras-dependent activation of Raf1. Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4. In addition, Sprouty4 mutants of the amino-terminal region containing the conserved tyrosine residue, which is necessary for suppressing fibroblast growth factor signalling, still inhibit the VEGF-induced ERK pathway. Our results show that receptor tyrosine kinases use distinct pathways for Raf and ERK activation and that Sprouty4 differentially regulates these pathways.</description><subject>Animals</subject><subject>Binding sites</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Developmental Biology</subject><subject>Endothelial Growth Factors - metabolism</subject><subject>Endothelial Growth Factors - pharmacology</subject><subject>Epidermal growth factor</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Eukaryotic Cells - cytology</subject><subject>Eukaryotic Cells - drug effects</subject><subject>Eukaryotic Cells - metabolism</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Fibroblast Growth Factors - pharmacology</subject><subject>Fibroblasts</subject><subject>Growth Substances - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Intercellular Signaling Peptides and Proteins - pharmacology</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Kinases</subject><subject>letter</subject><subject>Life Sciences</subject><subject>Lymphokines - metabolism</subject><subject>Lymphokines - pharmacology</subject><subject>Mammals</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - genetics</subject><subject>Mitogen-Activated Protein Kinases - genetics</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Mutation - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Protein Binding - drug effects</subject><subject>Protein Binding - genetics</subject><subject>Protein kinases</subject><subject>Protein Structure, Tertiary - drug effects</subject><subject>Protein Structure, Tertiary - genetics</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-raf - genetics</subject><subject>Proto-Oncogene Proteins c-raf - metabolism</subject><subject>ras Proteins - genetics</subject><subject>ras Proteins - metabolism</subject><subject>Receptor Protein-Tyrosine Kinases - drug effects</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - genetics</subject><subject>Stem Cells</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascular Endothelial Growth Factors</subject><issn>1465-7392</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptke1r1TAUxoMo7kX9C0SKguKHzp68NO3HMaYOJ4M7_RzS9PSS0aZdkor3v18uLY6rJpCEPL_zcA4PIa-gOIOCVZ-caWpZPSHHwGWZ81LWT_fvUuSS1fSInIRwVxTAeSGfkyOgEiTn7JjcfNfDoHurXXY7-XGOO56FeZo8hoAh2-iQW9fihOlwMbvcfMu0ifaXjnZ0WbPLmiRbt83imOAOXpBnne4DvlzvU_Lz8-WPi6_59c2Xq4vz69xwUcbUlMS2AC3KphbCGANMdhTrSkrTYiN1XbESJAIFaA0YELVmXVMIMK2mVc1OyfvFNzV9P2OIarDBYN9rh-MclGSUCQp78O1f4N04e5d6UzStSlDKE_Rugba6R2VdN0avzd5RnUPFaCUryRJ19h8q7RYHa0aHnU3_BwUfDwoSE_F33Oo5BHV1uzlk14GMH0Pw2KnJ20H7nYJC7SNWS8QJfLMONDcDto_YmmkCPixASJLbon-c-B-r1wvpdJw9_rFa5Qfyo7TI</recordid><startdate>20030501</startdate><enddate>20030501</enddate><creator>Yoshimura, Akihiko</creator><creator>Sasaki, Atsuo</creator><creator>Taketomi, Takaharu</creator><creator>Kato, Reiko</creator><creator>Saeki, Kazuko</creator><creator>Nonami, Atsushi</creator><creator>Sasaki, Mika</creator><creator>Kuriyama, Masamitsu</creator><creator>Saito, Naoaki</creator><creator>Shibuya, Masabumi</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030501</creationdate><title>Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1</title><author>Yoshimura, Akihiko ; Sasaki, Atsuo ; Taketomi, Takaharu ; Kato, Reiko ; Saeki, Kazuko ; Nonami, Atsushi ; Sasaki, Mika ; Kuriyama, Masamitsu ; Saito, Naoaki ; Shibuya, Masabumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-737ed01a56b955ccc137f2e9877cdeb7a983617e1211dc1c159a3fb051cda2893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Binding sites</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer Research</topic><topic>Cell Biology</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Developmental Biology</topic><topic>Endothelial Growth Factors - metabolism</topic><topic>Endothelial Growth Factors - pharmacology</topic><topic>Epidermal growth factor</topic><topic>Epidermal Growth Factor - metabolism</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>Eukaryotic Cells - cytology</topic><topic>Eukaryotic Cells - drug effects</topic><topic>Eukaryotic Cells - metabolism</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Fibroblast Growth Factors - pharmacology</topic><topic>Fibroblasts</topic><topic>Growth Substances - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Intercellular Signaling Peptides and Proteins - pharmacology</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Kinases</topic><topic>letter</topic><topic>Life Sciences</topic><topic>Lymphokines - metabolism</topic><topic>Lymphokines - pharmacology</topic><topic>Mammals</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - genetics</topic><topic>Mitogen-Activated Protein Kinases - genetics</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Mutation - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Protein Binding - drug effects</topic><topic>Protein Binding - genetics</topic><topic>Protein kinases</topic><topic>Protein Structure, Tertiary - drug effects</topic><topic>Protein Structure, Tertiary - genetics</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-raf - genetics</topic><topic>Proto-Oncogene Proteins c-raf - metabolism</topic><topic>ras Proteins - genetics</topic><topic>ras Proteins - metabolism</topic><topic>Receptor Protein-Tyrosine Kinases - drug effects</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - genetics</topic><topic>Stem Cells</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascular Endothelial Growth Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoshimura, Akihiko</creatorcontrib><creatorcontrib>Sasaki, Atsuo</creatorcontrib><creatorcontrib>Taketomi, Takaharu</creatorcontrib><creatorcontrib>Kato, Reiko</creatorcontrib><creatorcontrib>Saeki, Kazuko</creatorcontrib><creatorcontrib>Nonami, Atsushi</creatorcontrib><creatorcontrib>Sasaki, Mika</creatorcontrib><creatorcontrib>Kuriyama, Masamitsu</creatorcontrib><creatorcontrib>Saito, Naoaki</creatorcontrib><creatorcontrib>Shibuya, Masabumi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</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>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoshimura, Akihiko</au><au>Sasaki, Atsuo</au><au>Taketomi, Takaharu</au><au>Kato, Reiko</au><au>Saeki, Kazuko</au><au>Nonami, Atsushi</au><au>Sasaki, Mika</au><au>Kuriyama, Masamitsu</au><au>Saito, Naoaki</au><au>Shibuya, Masabumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>5</volume><issue>5</issue><spage>427</spage><epage>432</epage><pages>427-432</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>The signalling cascade including Raf, mitogen-activated protein kinase (MAPK) kinase and extracellular-signal-regulated kinase (ERK) is important in many facets of cellular regulation. Raf is activated through both Ras-dependent and Ras-independent mechanisms, but the regulatory mechanisms of Raf activation remain unclear. Two families of membrane-bound molecules, Sprouty and Sprouty-related EVH1-domain-containing protein (Spred) have been identified and characterized as negative regulators of growth-factor-induced ERK activation. But the molecular functions of mammalian Sproutys have not been clarified. Here we show that mammalian Sprouty4 suppresses vascular epithelial growth factor (VEGF)-induced, Ras-independent activation of Raf1 but does not affect epidermal growth factor (EGF)-induced, Ras-dependent activation of Raf1. Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4. In addition, Sprouty4 mutants of the amino-terminal region containing the conserved tyrosine residue, which is necessary for suppressing fibroblast growth factor signalling, still inhibit the VEGF-induced ERK pathway. Our results show that receptor tyrosine kinases use distinct pathways for Raf and ERK activation and that Sprouty4 differentially regulates these pathways.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>12717443</pmid><doi>10.1038/ncb978</doi><tpages>6</tpages></addata></record>
fulltext fulltext
identifier ISSN: 1465-7392
ispartof Nature cell biology, 2003-05, Vol.5 (5), p.427-432
issn 1465-7392
1476-4679
language eng
recordid cdi_proquest_miscellaneous_73235219
source MEDLINE; Nature; Alma/SFX Local Collection
subjects Animals
Binding sites
Biomedical and Life Sciences
Cancer Research
Cell Biology
Cell Membrane - drug effects
Cell Membrane - metabolism
Developmental Biology
Endothelial Growth Factors - metabolism
Endothelial Growth Factors - pharmacology
Epidermal growth factor
Epidermal Growth Factor - metabolism
Epidermal Growth Factor - pharmacology
Eukaryotic Cells - cytology
Eukaryotic Cells - drug effects
Eukaryotic Cells - metabolism
Fibroblast Growth Factors - metabolism
Fibroblast Growth Factors - pharmacology
Fibroblasts
Growth Substances - metabolism
Humans
Immunohistochemistry
Intercellular Signaling Peptides and Proteins - metabolism
Intercellular Signaling Peptides and Proteins - pharmacology
Intracellular Signaling Peptides and Proteins
Kinases
letter
Life Sciences
Lymphokines - metabolism
Lymphokines - pharmacology
Mammals
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - genetics
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Mutation - genetics
Nerve Tissue Proteins - metabolism
Phosphorylation
Physiological aspects
Protein Binding - drug effects
Protein Binding - genetics
Protein kinases
Protein Structure, Tertiary - drug effects
Protein Structure, Tertiary - genetics
Proteins
Proto-Oncogene Proteins c-raf - genetics
Proto-Oncogene Proteins c-raf - metabolism
ras Proteins - genetics
ras Proteins - metabolism
Receptor Protein-Tyrosine Kinases - drug effects
Receptor Protein-Tyrosine Kinases - metabolism
Signal Transduction - drug effects
Signal Transduction - genetics
Stem Cells
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
title Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T14%3A21%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mammalian%20Sprouty4%20suppresses%20Ras-independent%20ERK%20activation%20by%20binding%20to%20Raf1&rft.jtitle=Nature%20cell%20biology&rft.au=Yoshimura,%20Akihiko&rft.date=2003-05-01&rft.volume=5&rft.issue=5&rft.spage=427&rft.epage=432&rft.pages=427-432&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/ncb978&rft_dat=%3Cgale_proqu%3EA183287873%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222285224&rft_id=info:pmid/12717443&rft_galeid=A183287873&rfr_iscdi=true