Morphogenesis of human endothelial cells is inhibited by DAB2 via Src
Disabled-2 (DAB2) is an adaptor protein implicated in signal transduction pathways and in protein traffic regulation. Here, we show that DAB2 is highly expressed in human endothelial cells. DAB2 silencing in endothelial cells by lentiviral-mediated small hairpin RNA expression affects cell migration...
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| Veröffentlicht in: | FEBS letters 2008-07, Vol.582 (17), p.2542-2548 |
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| creator | Orlandini, Maurizio Nucciotti, Sara Galvagni, Federico Bardelli, Monia Rocchigiani, Marina Petraglia, Felice Oliviero, Salvatore |
| description | Disabled-2 (DAB2) is an adaptor protein implicated in signal transduction pathways and in protein traffic regulation. Here, we show that DAB2 is highly expressed in human endothelial cells. DAB2 silencing in endothelial cells by lentiviral-mediated small hairpin RNA expression affects cell migration and differentiation into capillary-like structures while increasing cell proliferation and viability. DAB2 knockdown causes activation of the Src-FAK signal pathway, extracellular-signal regulated kinase and c-Jun NH2-terminal kinase activation, and inhibition of p38 phosphorylation. In DAB2 silenced endothelial cells, pharmacological inhibition of Src with its specific inhibitor PP2 abolishes focal adhesion kinase activation and restores differentiation of endothelial cells. These results suggest that DAB2, via Src and focal adhesion signaling, plays a role in human endothelial cell function. |
| doi_str_mv | 10.1016/j.febslet.2008.06.025 |
| format | Article |
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Here, we show that DAB2 is highly expressed in human endothelial cells. DAB2 silencing in endothelial cells by lentiviral-mediated small hairpin RNA expression affects cell migration and differentiation into capillary-like structures while increasing cell proliferation and viability. DAB2 knockdown causes activation of the Src-FAK signal pathway, extracellular-signal regulated kinase and c-Jun NH2-terminal kinase activation, and inhibition of p38 phosphorylation. In DAB2 silenced endothelial cells, pharmacological inhibition of Src with its specific inhibitor PP2 abolishes focal adhesion kinase activation and restores differentiation of endothelial cells. 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Here, we show that DAB2 is highly expressed in human endothelial cells. DAB2 silencing in endothelial cells by lentiviral-mediated small hairpin RNA expression affects cell migration and differentiation into capillary-like structures while increasing cell proliferation and viability. DAB2 knockdown causes activation of the Src-FAK signal pathway, extracellular-signal regulated kinase and c-Jun NH2-terminal kinase activation, and inhibition of p38 phosphorylation. In DAB2 silenced endothelial cells, pharmacological inhibition of Src with its specific inhibitor PP2 abolishes focal adhesion kinase activation and restores differentiation of endothelial cells. These results suggest that DAB2, via Src and focal adhesion signaling, plays a role in human endothelial cell function.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - physiology</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>c-Jun NH2-terminal kinase</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Movement - genetics</subject><subject>Cells, Cultured</subject><subject>DAB2</subject><subject>Disabled-2</subject><subject>Endothelium, Vascular - growth & development</subject><subject>Endothelium, Vascular - metabolism</subject><subject>ERK</subject><subject>extracellular-signal regulated kinase</subject><subject>FAK</subject><subject>Focal adhesion kinase</subject><subject>Focal Adhesion Kinase 1 - genetics</subject><subject>Focal Adhesion Kinase 1 - metabolism</subject><subject>Gene Silencing</subject><subject>human umbilical vein endothelial cells</subject><subject>Humans</subject><subject>HUVEC</subject><subject>JNK</subject><subject>MAPK</subject><subject>Mice</subject><subject>Mitogen-activated protein kinase</subject><subject>Mitogen-Activated Protein Kinase Kinases - metabolism</subject><subject>Morphogenesis</subject><subject>Neovascularization, Physiologic - genetics</subject><subject>RNA interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>Src</subject><subject>src-Family Kinases - antagonists & inhibitors</subject><subject>src-Family Kinases - metabolism</subject><subject>Tumor Suppressor Proteins</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS0EokvhI4B84pYw_pvJCbVlS5GKOBTOluNMWK-yyWJnW-23J9GuxLGcrJHfvHnzG8beCygFCPtpW3bU5J6mUgJgCbYEaV6wlcBKFUpbfMlWAEIXpqrVBXuT8xbmGkX9ml0INCi1NSu2_j6m_Wb8TQPlmPnY8c1h5wdOQztOG-qj73mgvs98_o3DJjZxopY3R_7l6lryx-j5Qwpv2avO95nend9L9ut2_fPmrrj_8fXbzdV9EQxYVXRBUtVBZTwFoSrrg4BWesSqsWBAGMTgNbSkpEWwoTaoDJI2Gq3A0KlL9vHku0_jnwPlye1iXuL5gcZDdrZW8_6onxWK2oLSSs1CcxKGNOacqHP7FHc-HZ0At4B2W3cG7RbQDqybQc99H84DDs2O2n9dZ7Kz4O4keIo9Hf_P1d2ur-XDcrXlaIAARuol4-eTFc1oHyMll0OkIVAbE4XJtWN8Ju1fXRekzg</recordid><startdate>20080723</startdate><enddate>20080723</enddate><creator>Orlandini, Maurizio</creator><creator>Nucciotti, Sara</creator><creator>Galvagni, Federico</creator><creator>Bardelli, Monia</creator><creator>Rocchigiani, Marina</creator><creator>Petraglia, Felice</creator><creator>Oliviero, Salvatore</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20080723</creationdate><title>Morphogenesis of human endothelial cells is inhibited by DAB2 via Src</title><author>Orlandini, Maurizio ; Nucciotti, Sara ; Galvagni, Federico ; Bardelli, Monia ; Rocchigiani, Marina ; Petraglia, Felice ; Oliviero, Salvatore</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5063-fc2e7f075aec1376ac10d2a887b60501588ca40de326806c958358e4548618cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adaptor Proteins, Signal Transducing - physiology</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>c-Jun NH2-terminal kinase</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Movement - genetics</topic><topic>Cells, Cultured</topic><topic>DAB2</topic><topic>Disabled-2</topic><topic>Endothelium, Vascular - growth & development</topic><topic>Endothelium, Vascular - metabolism</topic><topic>ERK</topic><topic>extracellular-signal regulated kinase</topic><topic>FAK</topic><topic>Focal adhesion kinase</topic><topic>Focal Adhesion Kinase 1 - genetics</topic><topic>Focal Adhesion Kinase 1 - metabolism</topic><topic>Gene Silencing</topic><topic>human umbilical vein endothelial cells</topic><topic>Humans</topic><topic>HUVEC</topic><topic>JNK</topic><topic>MAPK</topic><topic>Mice</topic><topic>Mitogen-activated protein kinase</topic><topic>Mitogen-Activated Protein Kinase Kinases - metabolism</topic><topic>Morphogenesis</topic><topic>Neovascularization, Physiologic - genetics</topic><topic>RNA interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>Src</topic><topic>src-Family Kinases - antagonists & inhibitors</topic><topic>src-Family Kinases - metabolism</topic><topic>Tumor Suppressor Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orlandini, Maurizio</creatorcontrib><creatorcontrib>Nucciotti, Sara</creatorcontrib><creatorcontrib>Galvagni, Federico</creatorcontrib><creatorcontrib>Bardelli, Monia</creatorcontrib><creatorcontrib>Rocchigiani, Marina</creatorcontrib><creatorcontrib>Petraglia, Felice</creatorcontrib><creatorcontrib>Oliviero, Salvatore</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orlandini, Maurizio</au><au>Nucciotti, Sara</au><au>Galvagni, Federico</au><au>Bardelli, Monia</au><au>Rocchigiani, Marina</au><au>Petraglia, Felice</au><au>Oliviero, Salvatore</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Morphogenesis of human endothelial cells is inhibited by DAB2 via Src</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2008-07-23</date><risdate>2008</risdate><volume>582</volume><issue>17</issue><spage>2542</spage><epage>2548</epage><pages>2542-2548</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>Disabled-2 (DAB2) is an adaptor protein implicated in signal transduction pathways and in protein traffic regulation. Here, we show that DAB2 is highly expressed in human endothelial cells. DAB2 silencing in endothelial cells by lentiviral-mediated small hairpin RNA expression affects cell migration and differentiation into capillary-like structures while increasing cell proliferation and viability. DAB2 knockdown causes activation of the Src-FAK signal pathway, extracellular-signal regulated kinase and c-Jun NH2-terminal kinase activation, and inhibition of p38 phosphorylation. In DAB2 silenced endothelial cells, pharmacological inhibition of Src with its specific inhibitor PP2 abolishes focal adhesion kinase activation and restores differentiation of endothelial cells. These results suggest that DAB2, via Src and focal adhesion signaling, plays a role in human endothelial cell function.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>18582465</pmid><doi>10.1016/j.febslet.2008.06.025</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - physiology Angiogenesis Animals c-Jun NH2-terminal kinase Cell Differentiation - genetics Cell Movement - genetics Cells, Cultured DAB2 Disabled-2 Endothelium, Vascular - growth & development Endothelium, Vascular - metabolism ERK extracellular-signal regulated kinase FAK Focal adhesion kinase Focal Adhesion Kinase 1 - genetics Focal Adhesion Kinase 1 - metabolism Gene Silencing human umbilical vein endothelial cells Humans HUVEC JNK MAPK Mice Mitogen-activated protein kinase Mitogen-Activated Protein Kinase Kinases - metabolism Morphogenesis Neovascularization, Physiologic - genetics RNA interference RNA, Small Interfering - genetics Src src-Family Kinases - antagonists & inhibitors src-Family Kinases - metabolism Tumor Suppressor Proteins |
| title | Morphogenesis of human endothelial cells is inhibited by DAB2 via Src |
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