Repression of c-Cbl leads to enhanced G-CSF Jak-STAT signaling without increased cell proliferation
Engagement of the Granulocyte-Colony-Stimulating Factor (G-CSF) receptor activates non-receptor protein tyrosine kinases Lyn and Jak2. We found that Lyn-deficient DT40 cells that express the G-CSF receptor (DT40GR) do not demonstrate G-CSF-induced mitogenic signaling. Lyn associates with and phospho...
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| Veröffentlicht in: | Oncogene 2002-08, Vol.21 (34), p.5346-5355 |
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| creator | LIN WANG RUDERT, William A LOUTAEV, Inna ROGINSKAYA, Vera COREY, Seth J |
| description | Engagement of the Granulocyte-Colony-Stimulating Factor (G-CSF) receptor activates non-receptor protein tyrosine kinases Lyn and Jak2. We found that Lyn-deficient DT40 cells that express the G-CSF receptor (DT40GR) do not demonstrate G-CSF-induced mitogenic signaling. Lyn associates with and phosphorylates a small set of molecules, including c-Cbl. c-Cbl is an adaptor involved in cell growth and cytoskeletal reorganization, predominantly in hematopoietic cells. Using yeast two-hybrid analysis, we found that c-Cbl directly couples Lyn to PI 3-kinase. We also found that expression of the c-CblY731F mutant, which uncouples PI 3-kinase, resulted in the inhibition of G-CSF-induced proliferative signaling in DT40GR cells. As a complementary strategy, we sought to analyse the effects of c-Cbl deficiency in DT40GR cells. We isolated, cloned and sequenced the full-length cDNA for chicken c-Cbl and constructed antisense vectors. Antisense inhibition of c-Cbl expression in DT40GR cells led to enhanced Jak-STAT activation following G-CSF stimulation. Yet, this enhancement of Jak-STAT activation was associated with decreased G-CSF-induced PI 3-kinase activity and DNA synthesis. PI 3-kinase activity correlated with DNA synthesis and physiological levels of c-Cbl. Together, these data suggest that physiologic level of c-Cbl provides a growth stimulatory pathway for G-CSF and that enhanced Jak-STAT activation is not sufficient for G-CSF-induced growth. |
| doi_str_mv | 10.1038/sj.onc.1205670 |
| format | Article |
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We found that Lyn-deficient DT40 cells that express the G-CSF receptor (DT40GR) do not demonstrate G-CSF-induced mitogenic signaling. Lyn associates with and phosphorylates a small set of molecules, including c-Cbl. c-Cbl is an adaptor involved in cell growth and cytoskeletal reorganization, predominantly in hematopoietic cells. Using yeast two-hybrid analysis, we found that c-Cbl directly couples Lyn to PI 3-kinase. We also found that expression of the c-CblY731F mutant, which uncouples PI 3-kinase, resulted in the inhibition of G-CSF-induced proliferative signaling in DT40GR cells. As a complementary strategy, we sought to analyse the effects of c-Cbl deficiency in DT40GR cells. We isolated, cloned and sequenced the full-length cDNA for chicken c-Cbl and constructed antisense vectors. Antisense inhibition of c-Cbl expression in DT40GR cells led to enhanced Jak-STAT activation following G-CSF stimulation. Yet, this enhancement of Jak-STAT activation was associated with decreased G-CSF-induced PI 3-kinase activity and DNA synthesis. PI 3-kinase activity correlated with DNA synthesis and physiological levels of c-Cbl. Together, these data suggest that physiologic level of c-Cbl provides a growth stimulatory pathway for G-CSF and that enhanced Jak-STAT activation is not sufficient for G-CSF-induced growth.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1205670</identifier><identifier>PMID: 12149655</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adaptor proteins ; Amino Acid Sequence ; Analysis ; Animals ; Base Sequence ; Biological and medical sciences ; Blotting, Northern ; Caenorhabditis elegans ; Cbl protein ; Cell Division ; Cell growth ; Cell physiology ; Cell proliferation ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Chickens ; Cloning, Molecular ; Colony-stimulating factor ; Colony-stimulating factors (Physiology) ; Cytoskeleton ; Deoxyribonucleic acid ; DNA ; DNA biosynthesis ; DNA Primers - chemistry ; DNA synthesis ; DNA-Binding Proteins - metabolism ; Drosophila ; Expression vectors ; Fundamental and applied biological sciences. Psychology ; Granulocyte colony-stimulating factor ; Granulocyte Colony-Stimulating Factor - metabolism ; Guanosine Triphosphate - metabolism ; Humans ; Janus Kinase 2 ; Kinases ; Leukocytes (granulocytic) ; Lyn protein ; Mice ; Milk Proteins ; Molecular and cellular biology ; Molecular Sequence Data ; Oligonucleotides, Antisense - pharmacology ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphotransferases ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases - metabolism ; Proto-Oncogene Proteins - physiology ; Proto-Oncogene Proteins c-cbl ; Receptors, Granulocyte Colony-Stimulating Factor - metabolism ; Sequence Homology, Amino Acid ; Signal transduction ; Signal Transduction - physiology ; src-Family Kinases - metabolism ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; STAT5 Transcription Factor ; Trans-Activators - metabolism ; Tyrosine ; Ubiquitin-Protein Ligases</subject><ispartof>Oncogene, 2002-08, Vol.21 (34), p.5346-5355</ispartof><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 8, 2002</rights><rights>Macmillan Publishers Limited 2002.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-ee1a0c87c19f53d5c1a4e1add695b4a8a287739d89501f2130361ece9de9d0b33</citedby><cites>FETCH-LOGICAL-c552t-ee1a0c87c19f53d5c1a4e1add695b4a8a287739d89501f2130361ece9de9d0b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13852311$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12149655$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LIN WANG</creatorcontrib><creatorcontrib>RUDERT, William A</creatorcontrib><creatorcontrib>LOUTAEV, Inna</creatorcontrib><creatorcontrib>ROGINSKAYA, Vera</creatorcontrib><creatorcontrib>COREY, Seth J</creatorcontrib><title>Repression of c-Cbl leads to enhanced G-CSF Jak-STAT signaling without increased cell proliferation</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>Engagement of the Granulocyte-Colony-Stimulating Factor (G-CSF) receptor activates non-receptor protein tyrosine kinases Lyn and Jak2. We found that Lyn-deficient DT40 cells that express the G-CSF receptor (DT40GR) do not demonstrate G-CSF-induced mitogenic signaling. Lyn associates with and phosphorylates a small set of molecules, including c-Cbl. c-Cbl is an adaptor involved in cell growth and cytoskeletal reorganization, predominantly in hematopoietic cells. Using yeast two-hybrid analysis, we found that c-Cbl directly couples Lyn to PI 3-kinase. We also found that expression of the c-CblY731F mutant, which uncouples PI 3-kinase, resulted in the inhibition of G-CSF-induced proliferative signaling in DT40GR cells. As a complementary strategy, we sought to analyse the effects of c-Cbl deficiency in DT40GR cells. We isolated, cloned and sequenced the full-length cDNA for chicken c-Cbl and constructed antisense vectors. Antisense inhibition of c-Cbl expression in DT40GR cells led to enhanced Jak-STAT activation following G-CSF stimulation. Yet, this enhancement of Jak-STAT activation was associated with decreased G-CSF-induced PI 3-kinase activity and DNA synthesis. PI 3-kinase activity correlated with DNA synthesis and physiological levels of c-Cbl. Together, these data suggest that physiologic level of c-Cbl provides a growth stimulatory pathway for G-CSF and that enhanced Jak-STAT activation is not sufficient for G-CSF-induced growth.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adaptor proteins</subject><subject>Amino Acid Sequence</subject><subject>Analysis</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Caenorhabditis elegans</subject><subject>Cbl protein</subject><subject>Cell Division</subject><subject>Cell growth</subject><subject>Cell physiology</subject><subject>Cell proliferation</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Chickens</subject><subject>Cloning, Molecular</subject><subject>Colony-stimulating factor</subject><subject>Colony-stimulating factors (Physiology)</subject><subject>Cytoskeleton</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA Primers - chemistry</subject><subject>DNA synthesis</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drosophila</subject><subject>Expression vectors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Granulocyte colony-stimulating factor</subject><subject>Granulocyte Colony-Stimulating Factor - metabolism</subject><subject>Guanosine Triphosphate - metabolism</subject><subject>Humans</subject><subject>Janus Kinase 2</subject><subject>Kinases</subject><subject>Leukocytes (granulocytic)</subject><subject>Lyn protein</subject><subject>Mice</subject><subject>Milk Proteins</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphotransferases</subject><subject>Polymerase Chain Reaction</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins - physiology</subject><subject>Proto-Oncogene Proteins c-cbl</subject><subject>Receptors, Granulocyte Colony-Stimulating Factor - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Signal transduction</subject><subject>Signal Transduction - physiology</subject><subject>src-Family Kinases - metabolism</subject><subject>STAT1 Transcription Factor</subject><subject>STAT3 Transcription Factor</subject><subject>STAT5 Transcription Factor</subject><subject>Trans-Activators - metabolism</subject><subject>Tyrosine</subject><subject>Ubiquitin-Protein Ligases</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkdGLEzEQh4MoXj199VGCh75tzSSbzeaxFO88ORC8-hzS7GwvdZvUZJfD_96UWygIIgkEhm9-meEj5C2wJTDRfsr7ZQxuCZzJRrFnZAG1aiopdf2cLJiWrNJc8AvyKuc9Y0xpxl-SC-BQ60bKBXHf8ZgwZx8DjT111Xo70AFtl-kYKYYHGxx29KZa31_Tr_Zndb9ZbWj2u2AHH3b00Y8PcRqpDy6hzQV1OAz0mOLge0x2LMGvyYveDhnfzO8l-XH9ebP-Ut19u7ldr-4qJyUfK0SwzLXKge6l6KQDW5dS1zVabmvbWt4qJXTXlq2g5yCYaAAd6q5cthXiknx8yi2__5owj-bg82kcGzBO2SjQWqga_gtCK7Xk7Snx6i9wH6dUVs-GNyVIgBSyUO__SXFVoFq3BVo-QTs7oPGhj2OyrpwOD97FgL0v9VXxKLVitTo3uBRzTtibY_IHm34bYObk3uS9Ke7N7L40vJvHmLYH7M74LLsAH2bAZmeHPhW3Pp850UouAMQf0KS1JA</recordid><startdate>20020808</startdate><enddate>20020808</enddate><creator>LIN WANG</creator><creator>RUDERT, William A</creator><creator>LOUTAEV, Inna</creator><creator>ROGINSKAYA, Vera</creator><creator>COREY, Seth J</creator><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>3V.</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>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020808</creationdate><title>Repression of c-Cbl leads to enhanced G-CSF Jak-STAT signaling without increased cell proliferation</title><author>LIN WANG ; RUDERT, William A ; LOUTAEV, Inna ; ROGINSKAYA, Vera ; COREY, Seth J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-ee1a0c87c19f53d5c1a4e1add695b4a8a287739d89501f2130361ece9de9d0b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Adaptor proteins</topic><topic>Amino Acid Sequence</topic><topic>Analysis</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Caenorhabditis elegans</topic><topic>Cbl protein</topic><topic>Cell Division</topic><topic>Cell growth</topic><topic>Cell physiology</topic><topic>Cell proliferation</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Chickens</topic><topic>Cloning, Molecular</topic><topic>Colony-stimulating factor</topic><topic>Colony-stimulating factors (Physiology)</topic><topic>Cytoskeleton</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>DNA Primers - chemistry</topic><topic>DNA synthesis</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Drosophila</topic><topic>Expression vectors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Granulocyte colony-stimulating factor</topic><topic>Granulocyte Colony-Stimulating Factor - metabolism</topic><topic>Guanosine Triphosphate - metabolism</topic><topic>Humans</topic><topic>Janus Kinase 2</topic><topic>Kinases</topic><topic>Leukocytes (granulocytic)</topic><topic>Lyn protein</topic><topic>Mice</topic><topic>Milk Proteins</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Oligonucleotides, Antisense - pharmacology</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphotransferases</topic><topic>Polymerase Chain Reaction</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proto-Oncogene Proteins - physiology</topic><topic>Proto-Oncogene Proteins c-cbl</topic><topic>Receptors, Granulocyte Colony-Stimulating Factor - metabolism</topic><topic>Sequence Homology, Amino Acid</topic><topic>Signal transduction</topic><topic>Signal Transduction - physiology</topic><topic>src-Family Kinases - metabolism</topic><topic>STAT1 Transcription Factor</topic><topic>STAT3 Transcription Factor</topic><topic>STAT5 Transcription Factor</topic><topic>Trans-Activators - metabolism</topic><topic>Tyrosine</topic><topic>Ubiquitin-Protein Ligases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LIN WANG</creatorcontrib><creatorcontrib>RUDERT, William A</creatorcontrib><creatorcontrib>LOUTAEV, Inna</creatorcontrib><creatorcontrib>ROGINSKAYA, Vera</creatorcontrib><creatorcontrib>COREY, Seth J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & 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>Public Health Database</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>Research Library (Alumni Edition)</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>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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LIN WANG</au><au>RUDERT, William A</au><au>LOUTAEV, Inna</au><au>ROGINSKAYA, Vera</au><au>COREY, Seth J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repression of c-Cbl leads to enhanced G-CSF Jak-STAT signaling without increased cell proliferation</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2002-08-08</date><risdate>2002</risdate><volume>21</volume><issue>34</issue><spage>5346</spage><epage>5355</epage><pages>5346-5355</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Engagement of the Granulocyte-Colony-Stimulating Factor (G-CSF) receptor activates non-receptor protein tyrosine kinases Lyn and Jak2. We found that Lyn-deficient DT40 cells that express the G-CSF receptor (DT40GR) do not demonstrate G-CSF-induced mitogenic signaling. Lyn associates with and phosphorylates a small set of molecules, including c-Cbl. c-Cbl is an adaptor involved in cell growth and cytoskeletal reorganization, predominantly in hematopoietic cells. Using yeast two-hybrid analysis, we found that c-Cbl directly couples Lyn to PI 3-kinase. We also found that expression of the c-CblY731F mutant, which uncouples PI 3-kinase, resulted in the inhibition of G-CSF-induced proliferative signaling in DT40GR cells. As a complementary strategy, we sought to analyse the effects of c-Cbl deficiency in DT40GR cells. We isolated, cloned and sequenced the full-length cDNA for chicken c-Cbl and constructed antisense vectors. Antisense inhibition of c-Cbl expression in DT40GR cells led to enhanced Jak-STAT activation following G-CSF stimulation. Yet, this enhancement of Jak-STAT activation was associated with decreased G-CSF-induced PI 3-kinase activity and DNA synthesis. PI 3-kinase activity correlated with DNA synthesis and physiological levels of c-Cbl. Together, these data suggest that physiologic level of c-Cbl provides a growth stimulatory pathway for G-CSF and that enhanced Jak-STAT activation is not sufficient for G-CSF-induced growth.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>12149655</pmid><doi>10.1038/sj.onc.1205670</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase Adaptor proteins Amino Acid Sequence Analysis Animals Base Sequence Biological and medical sciences Blotting, Northern Caenorhabditis elegans Cbl protein Cell Division Cell growth Cell physiology Cell proliferation Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Chickens Cloning, Molecular Colony-stimulating factor Colony-stimulating factors (Physiology) Cytoskeleton Deoxyribonucleic acid DNA DNA biosynthesis DNA Primers - chemistry DNA synthesis DNA-Binding Proteins - metabolism Drosophila Expression vectors Fundamental and applied biological sciences. Psychology Granulocyte colony-stimulating factor Granulocyte Colony-Stimulating Factor - metabolism Guanosine Triphosphate - metabolism Humans Janus Kinase 2 Kinases Leukocytes (granulocytic) Lyn protein Mice Milk Proteins Molecular and cellular biology Molecular Sequence Data Oligonucleotides, Antisense - pharmacology Phosphatidylinositol 3-Kinases - metabolism Phosphotransferases Polymerase Chain Reaction Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins - physiology Proto-Oncogene Proteins c-cbl Receptors, Granulocyte Colony-Stimulating Factor - metabolism Sequence Homology, Amino Acid Signal transduction Signal Transduction - physiology src-Family Kinases - metabolism STAT1 Transcription Factor STAT3 Transcription Factor STAT5 Transcription Factor Trans-Activators - metabolism Tyrosine Ubiquitin-Protein Ligases |
| title | Repression of c-Cbl leads to enhanced G-CSF Jak-STAT signaling without increased cell proliferation |
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