Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis
Ephrin-B/EphB family proteins are implicated in bidirectional signaling and were initially defined through the function of their ectodomain sequences in activating EphB receptor tyrosine kinases. Ephrin-B1-3 are transmembrane proteins sharing highly conserved C-terminal cytoplasmic sequences. Here w...
Gespeichert in:
| Veröffentlicht in: | Journal of cell science 2002-08, Vol.115 (Pt 15), p.3073-3081 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3081 |
|---|---|
| container_issue | Pt 15 |
| container_start_page | 3073 |
| container_title | Journal of cell science |
| container_volume | 115 |
| creator | Huynh-Do, Uyen Vindis, Cécile Liu, Hua Cerretti, Douglas Pat McGrew, Jeffrey T Enriquez, Miriam Chen, Jin Daniel, Thomas O |
| description | Ephrin-B/EphB family proteins are implicated in bidirectional signaling and were initially defined through the function of their ectodomain sequences in activating EphB receptor tyrosine kinases. Ephrin-B1-3 are transmembrane proteins sharing highly conserved C-terminal cytoplasmic sequences. Here we use a soluble EphB1 ectodomain fusion protein (EphB1/Fc) to demonstrate that ephrin-B1 transduces signals that regulate cell attachment and migration. EphB1/Fc induced endothelial ephrin-B1 tyrosine phosphorylation, migration and integrin-mediated (alpha(v)beta(3) and alpha(5)beta(1)) attachment and promoted neovascularization, in vivo, in a mouse corneal micropocket assay. Activation of ephrin-B1 by EphB1/Fc induced phosphorylation of p46 JNK but not ERK-1/2 or p38 MAPkinases. By contrast, mutant ephrin-B1s bearing either a cytoplasmic deletion (ephrin-B1DeltaCy) or a deletion of four C-terminal amino acids (ephrin-B1DeltaPDZbd) fail to activate p46 JNK. Transient expression of intact ephin-B1 conferred EphB1/Fc migration responses on CHO cells, whereas the ephrin-B1DeltaCy and ephrin-B1DeltaPDZbd mutants were inactive. Thus ephrin-B1 transduces 'outside-in' signals through C-terminal protein interactions that affect integrin-mediated attachment and migration. |
| doi_str_mv | 10.1242/jcs.115.15.3073 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71907847</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71907847</sourcerecordid><originalsourceid>FETCH-LOGICAL-c396t-2db87400289b542e01781e4617c4aee501158bb4da8dfe4062dbf3dc456fccc53</originalsourceid><addsrcrecordid>eNpFUE1LAzEQDaJorZ69SU6e3DazyW52j1rqBxS86Dlks7PblG62JqngvzelBWGGgeG9N_MeIXfAZpCLfL4xYQZQzFJxJvkZmYCQMquBy3MyYSyHrC44vyLXIWwYYzKv5SW5ghygYiWfEL3crb112TPQ6LUL7d5goMH2Tm8DjSPVJtofHZFaF7E_QAdsbVq0dLC919GO7pHqGLVZD-gi1a5N3duxR4fBhhty0SUtvD3NKfl6WX4u3rLVx-v74mmVGV6XMcvbppIifVzVTSFyZCArQFGCNEIjFizZrJpGtLpqOxSsTISOt0YUZWeMKfiUPBx1d3783mOIarDB4HarHY77oCTUTFZCJuD8CDR-DMFjp3beDtr_KmDqkKpKqap0TqU6pJoY9yfpfZPc_-NPMfI_ph90kw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71907847</pqid></control><display><type>article</type><title>Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Company of Biologists</source><creator>Huynh-Do, Uyen ; Vindis, Cécile ; Liu, Hua ; Cerretti, Douglas Pat ; McGrew, Jeffrey T ; Enriquez, Miriam ; Chen, Jin ; Daniel, Thomas O</creator><creatorcontrib>Huynh-Do, Uyen ; Vindis, Cécile ; Liu, Hua ; Cerretti, Douglas Pat ; McGrew, Jeffrey T ; Enriquez, Miriam ; Chen, Jin ; Daniel, Thomas O</creatorcontrib><description>Ephrin-B/EphB family proteins are implicated in bidirectional signaling and were initially defined through the function of their ectodomain sequences in activating EphB receptor tyrosine kinases. Ephrin-B1-3 are transmembrane proteins sharing highly conserved C-terminal cytoplasmic sequences. Here we use a soluble EphB1 ectodomain fusion protein (EphB1/Fc) to demonstrate that ephrin-B1 transduces signals that regulate cell attachment and migration. EphB1/Fc induced endothelial ephrin-B1 tyrosine phosphorylation, migration and integrin-mediated (alpha(v)beta(3) and alpha(5)beta(1)) attachment and promoted neovascularization, in vivo, in a mouse corneal micropocket assay. Activation of ephrin-B1 by EphB1/Fc induced phosphorylation of p46 JNK but not ERK-1/2 or p38 MAPkinases. By contrast, mutant ephrin-B1s bearing either a cytoplasmic deletion (ephrin-B1DeltaCy) or a deletion of four C-terminal amino acids (ephrin-B1DeltaPDZbd) fail to activate p46 JNK. Transient expression of intact ephin-B1 conferred EphB1/Fc migration responses on CHO cells, whereas the ephrin-B1DeltaCy and ephrin-B1DeltaPDZbd mutants were inactive. Thus ephrin-B1 transduces 'outside-in' signals through C-terminal protein interactions that affect integrin-mediated attachment and migration.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.115.15.3073</identifier><identifier>PMID: 12118063</identifier><language>eng</language><publisher>England</publisher><subject>Amino Acid Sequence - genetics ; Animals ; Cell Adhesion - genetics ; Cell Membrane - metabolism ; Cell Movement - genetics ; CHO Cells ; Cornea - blood supply ; Cornea - growth & development ; Cornea - metabolism ; Cricetinae ; Endothelium, Vascular - cytology ; Endothelium, Vascular - metabolism ; Ephrin-B1 - deficiency ; Ephrin-B1 - genetics ; Humans ; Integrins - genetics ; Integrins - metabolism ; Male ; MAP Kinase Signaling System - genetics ; Mice ; Mutation - genetics ; Neovascularization, Physiologic - genetics ; Organ Culture Techniques ; Phosphorylation ; Protein Structure, Tertiary - genetics ; Receptor, EphB1 - genetics ; Receptor, EphB1 - metabolism ; Recombinant Fusion Proteins ; Signal Transduction - genetics</subject><ispartof>Journal of cell science, 2002-08, Vol.115 (Pt 15), p.3073-3081</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-2db87400289b542e01781e4617c4aee501158bb4da8dfe4062dbf3dc456fccc53</citedby><cites>FETCH-LOGICAL-c396t-2db87400289b542e01781e4617c4aee501158bb4da8dfe4062dbf3dc456fccc53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3665,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12118063$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huynh-Do, Uyen</creatorcontrib><creatorcontrib>Vindis, Cécile</creatorcontrib><creatorcontrib>Liu, Hua</creatorcontrib><creatorcontrib>Cerretti, Douglas Pat</creatorcontrib><creatorcontrib>McGrew, Jeffrey T</creatorcontrib><creatorcontrib>Enriquez, Miriam</creatorcontrib><creatorcontrib>Chen, Jin</creatorcontrib><creatorcontrib>Daniel, Thomas O</creatorcontrib><title>Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis</title><title>Journal of cell science</title><addtitle>J Cell Sci</addtitle><description>Ephrin-B/EphB family proteins are implicated in bidirectional signaling and were initially defined through the function of their ectodomain sequences in activating EphB receptor tyrosine kinases. Ephrin-B1-3 are transmembrane proteins sharing highly conserved C-terminal cytoplasmic sequences. Here we use a soluble EphB1 ectodomain fusion protein (EphB1/Fc) to demonstrate that ephrin-B1 transduces signals that regulate cell attachment and migration. EphB1/Fc induced endothelial ephrin-B1 tyrosine phosphorylation, migration and integrin-mediated (alpha(v)beta(3) and alpha(5)beta(1)) attachment and promoted neovascularization, in vivo, in a mouse corneal micropocket assay. Activation of ephrin-B1 by EphB1/Fc induced phosphorylation of p46 JNK but not ERK-1/2 or p38 MAPkinases. By contrast, mutant ephrin-B1s bearing either a cytoplasmic deletion (ephrin-B1DeltaCy) or a deletion of four C-terminal amino acids (ephrin-B1DeltaPDZbd) fail to activate p46 JNK. Transient expression of intact ephin-B1 conferred EphB1/Fc migration responses on CHO cells, whereas the ephrin-B1DeltaCy and ephrin-B1DeltaPDZbd mutants were inactive. Thus ephrin-B1 transduces 'outside-in' signals through C-terminal protein interactions that affect integrin-mediated attachment and migration.</description><subject>Amino Acid Sequence - genetics</subject><subject>Animals</subject><subject>Cell Adhesion - genetics</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Movement - genetics</subject><subject>CHO Cells</subject><subject>Cornea - blood supply</subject><subject>Cornea - growth & development</subject><subject>Cornea - metabolism</subject><subject>Cricetinae</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Ephrin-B1 - deficiency</subject><subject>Ephrin-B1 - genetics</subject><subject>Humans</subject><subject>Integrins - genetics</subject><subject>Integrins - metabolism</subject><subject>Male</subject><subject>MAP Kinase Signaling System - genetics</subject><subject>Mice</subject><subject>Mutation - genetics</subject><subject>Neovascularization, Physiologic - genetics</subject><subject>Organ Culture Techniques</subject><subject>Phosphorylation</subject><subject>Protein Structure, Tertiary - genetics</subject><subject>Receptor, EphB1 - genetics</subject><subject>Receptor, EphB1 - metabolism</subject><subject>Recombinant Fusion Proteins</subject><subject>Signal Transduction - genetics</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUE1LAzEQDaJorZ69SU6e3DazyW52j1rqBxS86Dlks7PblG62JqngvzelBWGGgeG9N_MeIXfAZpCLfL4xYQZQzFJxJvkZmYCQMquBy3MyYSyHrC44vyLXIWwYYzKv5SW5ghygYiWfEL3crb112TPQ6LUL7d5goMH2Tm8DjSPVJtofHZFaF7E_QAdsbVq0dLC919GO7pHqGLVZD-gi1a5N3duxR4fBhhty0SUtvD3NKfl6WX4u3rLVx-v74mmVGV6XMcvbppIifVzVTSFyZCArQFGCNEIjFizZrJpGtLpqOxSsTISOt0YUZWeMKfiUPBx1d3783mOIarDB4HarHY77oCTUTFZCJuD8CDR-DMFjp3beDtr_KmDqkKpKqap0TqU6pJoY9yfpfZPc_-NPMfI_ph90kw</recordid><startdate>20020801</startdate><enddate>20020801</enddate><creator>Huynh-Do, Uyen</creator><creator>Vindis, Cécile</creator><creator>Liu, Hua</creator><creator>Cerretti, Douglas Pat</creator><creator>McGrew, Jeffrey T</creator><creator>Enriquez, Miriam</creator><creator>Chen, Jin</creator><creator>Daniel, Thomas O</creator><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>7X8</scope></search><sort><creationdate>20020801</creationdate><title>Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis</title><author>Huynh-Do, Uyen ; Vindis, Cécile ; Liu, Hua ; Cerretti, Douglas Pat ; McGrew, Jeffrey T ; Enriquez, Miriam ; Chen, Jin ; Daniel, Thomas O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-2db87400289b542e01781e4617c4aee501158bb4da8dfe4062dbf3dc456fccc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amino Acid Sequence - genetics</topic><topic>Animals</topic><topic>Cell Adhesion - genetics</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Movement - genetics</topic><topic>CHO Cells</topic><topic>Cornea - blood supply</topic><topic>Cornea - growth & development</topic><topic>Cornea - metabolism</topic><topic>Cricetinae</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Ephrin-B1 - deficiency</topic><topic>Ephrin-B1 - genetics</topic><topic>Humans</topic><topic>Integrins - genetics</topic><topic>Integrins - metabolism</topic><topic>Male</topic><topic>MAP Kinase Signaling System - genetics</topic><topic>Mice</topic><topic>Mutation - genetics</topic><topic>Neovascularization, Physiologic - genetics</topic><topic>Organ Culture Techniques</topic><topic>Phosphorylation</topic><topic>Protein Structure, Tertiary - genetics</topic><topic>Receptor, EphB1 - genetics</topic><topic>Receptor, EphB1 - metabolism</topic><topic>Recombinant Fusion Proteins</topic><topic>Signal Transduction - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huynh-Do, Uyen</creatorcontrib><creatorcontrib>Vindis, Cécile</creatorcontrib><creatorcontrib>Liu, Hua</creatorcontrib><creatorcontrib>Cerretti, Douglas Pat</creatorcontrib><creatorcontrib>McGrew, Jeffrey T</creatorcontrib><creatorcontrib>Enriquez, Miriam</creatorcontrib><creatorcontrib>Chen, Jin</creatorcontrib><creatorcontrib>Daniel, Thomas O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huynh-Do, Uyen</au><au>Vindis, Cécile</au><au>Liu, Hua</au><au>Cerretti, Douglas Pat</au><au>McGrew, Jeffrey T</au><au>Enriquez, Miriam</au><au>Chen, Jin</au><au>Daniel, Thomas O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2002-08-01</date><risdate>2002</risdate><volume>115</volume><issue>Pt 15</issue><spage>3073</spage><epage>3081</epage><pages>3073-3081</pages><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>Ephrin-B/EphB family proteins are implicated in bidirectional signaling and were initially defined through the function of their ectodomain sequences in activating EphB receptor tyrosine kinases. Ephrin-B1-3 are transmembrane proteins sharing highly conserved C-terminal cytoplasmic sequences. Here we use a soluble EphB1 ectodomain fusion protein (EphB1/Fc) to demonstrate that ephrin-B1 transduces signals that regulate cell attachment and migration. EphB1/Fc induced endothelial ephrin-B1 tyrosine phosphorylation, migration and integrin-mediated (alpha(v)beta(3) and alpha(5)beta(1)) attachment and promoted neovascularization, in vivo, in a mouse corneal micropocket assay. Activation of ephrin-B1 by EphB1/Fc induced phosphorylation of p46 JNK but not ERK-1/2 or p38 MAPkinases. By contrast, mutant ephrin-B1s bearing either a cytoplasmic deletion (ephrin-B1DeltaCy) or a deletion of four C-terminal amino acids (ephrin-B1DeltaPDZbd) fail to activate p46 JNK. Transient expression of intact ephin-B1 conferred EphB1/Fc migration responses on CHO cells, whereas the ephrin-B1DeltaCy and ephrin-B1DeltaPDZbd mutants were inactive. Thus ephrin-B1 transduces 'outside-in' signals through C-terminal protein interactions that affect integrin-mediated attachment and migration.</abstract><cop>England</cop><pmid>12118063</pmid><doi>10.1242/jcs.115.15.3073</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9533 |
| ispartof | Journal of cell science, 2002-08, Vol.115 (Pt 15), p.3073-3081 |
| issn | 0021-9533 1477-9137 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71907847 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Company of Biologists |
| subjects | Amino Acid Sequence - genetics Animals Cell Adhesion - genetics Cell Membrane - metabolism Cell Movement - genetics CHO Cells Cornea - blood supply Cornea - growth & development Cornea - metabolism Cricetinae Endothelium, Vascular - cytology Endothelium, Vascular - metabolism Ephrin-B1 - deficiency Ephrin-B1 - genetics Humans Integrins - genetics Integrins - metabolism Male MAP Kinase Signaling System - genetics Mice Mutation - genetics Neovascularization, Physiologic - genetics Organ Culture Techniques Phosphorylation Protein Structure, Tertiary - genetics Receptor, EphB1 - genetics Receptor, EphB1 - metabolism Recombinant Fusion Proteins Signal Transduction - genetics |
| title | Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T04%3A01%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ephrin-B1%20transduces%20signals%20to%20activate%20integrin-mediated%20migration,%20attachment%20and%20angiogenesis&rft.jtitle=Journal%20of%20cell%20science&rft.au=Huynh-Do,%20Uyen&rft.date=2002-08-01&rft.volume=115&rft.issue=Pt%2015&rft.spage=3073&rft.epage=3081&rft.pages=3073-3081&rft.issn=0021-9533&rft.eissn=1477-9137&rft_id=info:doi/10.1242/jcs.115.15.3073&rft_dat=%3Cproquest_cross%3E71907847%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=71907847&rft_id=info:pmid/12118063&rfr_iscdi=true |