Breaking the integrin hinge. A defined structural constraint regulates integrin signaling
Integrins are heterodimeric (alpha, beta) cell adhesion receptors. We demonstrate that point mutations in the cytoplasmic domains of both the alpha and beta subunits promote constitutive signaling by the integrin alphaIIbbeta3. By generating charge reversal mutations, we show these "activating&...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 1996-03, Vol.271 (12), p.6571-6574 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6574 |
|---|---|
| container_issue | 12 |
| container_start_page | 6571 |
| container_title | The Journal of biological chemistry |
| container_volume | 271 |
| creator | Hughes, P E Diaz-Gonzalez, F Leong, L Wu, C McDonald, J A Shattil, S J Ginsberg, M H |
| description | Integrins are heterodimeric (alpha, beta) cell adhesion receptors. We demonstrate that point mutations in the cytoplasmic domains of both the alpha and beta subunits promote constitutive signaling by the integrin alphaIIbbeta3. By generating charge reversal mutations, we show these "activating" mutations may act by disrupting a potential salt bridge between the membrane-proximal portions of the alpha and beta subunit cytoplasmic domains. Thus, the modulation of specific interactions between the alpha and beta subunit cytoplasmic domains may regulate transmembrane signaling through integrins. In addition, these activating mutations induce dominant alterations in cellular behavior, such as the assembly of the extracellular matrix. Consequently, somatic mutations in integrin cytoplasmic domains could have profound effects in vivo on integrin-dependent functions such as matrix assembly, cell migration, and anchorage-dependent cell growth and survival. |
| doi_str_mv | 10.1074/jbc.271.12.6571 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_15599089</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>15599089</sourcerecordid><originalsourceid>FETCH-LOGICAL-p237t-f2386a4b6a817d7968334fa89cc2466a4282f2ea46406c5a3fb829a4407242ea3</originalsourceid><addsrcrecordid>eNpFkDtPwzAUhT2ASinMTEie2BL8ih9jqXhJlVhgYIoc5yZNSd1iOwP_HktE4i5H99zvnOEidENJSYkS9_vGlUzRkrJSVoqeoSUhjBaGVfoCXca4J3mEoQu00JJLIvUSfT4EsF-D73HaAR58gj4MHu-yAyVe4xa6wUOLYwqTS1OwI3ZHnzebWRygn0abIP4n49B7O-b4FTrv7BjhetYV-nh6fN-8FNu359fNelucGFep6BjX0opGWk1Vq4zUnIvOauMcEzJfmGYdAyukINJVlneNZsYKQRQT2ecrdPfXewrH7wliqg9DdDCO1sNxijWtKmOINhm8ncGpOUBbn8JwsOGnnn_BfwFgXV9_</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>15599089</pqid></control><display><type>article</type><title>Breaking the integrin hinge. A defined structural constraint regulates integrin signaling</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Hughes, P E ; Diaz-Gonzalez, F ; Leong, L ; Wu, C ; McDonald, J A ; Shattil, S J ; Ginsberg, M H</creator><creatorcontrib>Hughes, P E ; Diaz-Gonzalez, F ; Leong, L ; Wu, C ; McDonald, J A ; Shattil, S J ; Ginsberg, M H</creatorcontrib><description>Integrins are heterodimeric (alpha, beta) cell adhesion receptors. We demonstrate that point mutations in the cytoplasmic domains of both the alpha and beta subunits promote constitutive signaling by the integrin alphaIIbbeta3. By generating charge reversal mutations, we show these "activating" mutations may act by disrupting a potential salt bridge between the membrane-proximal portions of the alpha and beta subunit cytoplasmic domains. Thus, the modulation of specific interactions between the alpha and beta subunit cytoplasmic domains may regulate transmembrane signaling through integrins. In addition, these activating mutations induce dominant alterations in cellular behavior, such as the assembly of the extracellular matrix. Consequently, somatic mutations in integrin cytoplasmic domains could have profound effects in vivo on integrin-dependent functions such as matrix assembly, cell migration, and anchorage-dependent cell growth and survival.</description><identifier>ISSN: 0021-9258</identifier><identifier>DOI: 10.1074/jbc.271.12.6571</identifier><identifier>PMID: 8636068</identifier><language>eng</language><publisher>United States</publisher><subject>Amino Acid Sequence ; Animals ; Cell Adhesion Molecules - metabolism ; Cricetinae ; DNA, Complementary ; Focal Adhesion Protein-Tyrosine Kinases ; Integrins - chemistry ; Integrins - genetics ; Integrins - metabolism ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Phosphorylation ; Point Mutation ; Protein Conformation ; Protein-Tyrosine Kinases - metabolism ; Signal Transduction</subject><ispartof>The Journal of biological chemistry, 1996-03, Vol.271 (12), p.6571-6574</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8636068$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hughes, P E</creatorcontrib><creatorcontrib>Diaz-Gonzalez, F</creatorcontrib><creatorcontrib>Leong, L</creatorcontrib><creatorcontrib>Wu, C</creatorcontrib><creatorcontrib>McDonald, J A</creatorcontrib><creatorcontrib>Shattil, S J</creatorcontrib><creatorcontrib>Ginsberg, M H</creatorcontrib><title>Breaking the integrin hinge. A defined structural constraint regulates integrin signaling</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Integrins are heterodimeric (alpha, beta) cell adhesion receptors. We demonstrate that point mutations in the cytoplasmic domains of both the alpha and beta subunits promote constitutive signaling by the integrin alphaIIbbeta3. By generating charge reversal mutations, we show these "activating" mutations may act by disrupting a potential salt bridge between the membrane-proximal portions of the alpha and beta subunit cytoplasmic domains. Thus, the modulation of specific interactions between the alpha and beta subunit cytoplasmic domains may regulate transmembrane signaling through integrins. In addition, these activating mutations induce dominant alterations in cellular behavior, such as the assembly of the extracellular matrix. Consequently, somatic mutations in integrin cytoplasmic domains could have profound effects in vivo on integrin-dependent functions such as matrix assembly, cell migration, and anchorage-dependent cell growth and survival.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cricetinae</subject><subject>DNA, Complementary</subject><subject>Focal Adhesion Protein-Tyrosine Kinases</subject><subject>Integrins - chemistry</subject><subject>Integrins - genetics</subject><subject>Integrins - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Phosphorylation</subject><subject>Point Mutation</subject><subject>Protein Conformation</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Signal Transduction</subject><issn>0021-9258</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkDtPwzAUhT2ASinMTEie2BL8ih9jqXhJlVhgYIoc5yZNSd1iOwP_HktE4i5H99zvnOEidENJSYkS9_vGlUzRkrJSVoqeoSUhjBaGVfoCXca4J3mEoQu00JJLIvUSfT4EsF-D73HaAR58gj4MHu-yAyVe4xa6wUOLYwqTS1OwI3ZHnzebWRygn0abIP4n49B7O-b4FTrv7BjhetYV-nh6fN-8FNu359fNelucGFep6BjX0opGWk1Vq4zUnIvOauMcEzJfmGYdAyukINJVlneNZsYKQRQT2ecrdPfXewrH7wliqg9DdDCO1sNxijWtKmOINhm8ncGpOUBbn8JwsOGnnn_BfwFgXV9_</recordid><startdate>19960322</startdate><enddate>19960322</enddate><creator>Hughes, P E</creator><creator>Diaz-Gonzalez, F</creator><creator>Leong, L</creator><creator>Wu, C</creator><creator>McDonald, J A</creator><creator>Shattil, S J</creator><creator>Ginsberg, M H</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>19960322</creationdate><title>Breaking the integrin hinge. A defined structural constraint regulates integrin signaling</title><author>Hughes, P E ; Diaz-Gonzalez, F ; Leong, L ; Wu, C ; McDonald, J A ; Shattil, S J ; Ginsberg, M H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p237t-f2386a4b6a817d7968334fa89cc2466a4282f2ea46406c5a3fb829a4407242ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cricetinae</topic><topic>DNA, Complementary</topic><topic>Focal Adhesion Protein-Tyrosine Kinases</topic><topic>Integrins - chemistry</topic><topic>Integrins - genetics</topic><topic>Integrins - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Phosphorylation</topic><topic>Point Mutation</topic><topic>Protein Conformation</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hughes, P E</creatorcontrib><creatorcontrib>Diaz-Gonzalez, F</creatorcontrib><creatorcontrib>Leong, L</creatorcontrib><creatorcontrib>Wu, C</creatorcontrib><creatorcontrib>McDonald, J A</creatorcontrib><creatorcontrib>Shattil, S J</creatorcontrib><creatorcontrib>Ginsberg, M H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hughes, P E</au><au>Diaz-Gonzalez, F</au><au>Leong, L</au><au>Wu, C</au><au>McDonald, J A</au><au>Shattil, S J</au><au>Ginsberg, M H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Breaking the integrin hinge. A defined structural constraint regulates integrin signaling</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1996-03-22</date><risdate>1996</risdate><volume>271</volume><issue>12</issue><spage>6571</spage><epage>6574</epage><pages>6571-6574</pages><issn>0021-9258</issn><abstract>Integrins are heterodimeric (alpha, beta) cell adhesion receptors. We demonstrate that point mutations in the cytoplasmic domains of both the alpha and beta subunits promote constitutive signaling by the integrin alphaIIbbeta3. By generating charge reversal mutations, we show these "activating" mutations may act by disrupting a potential salt bridge between the membrane-proximal portions of the alpha and beta subunit cytoplasmic domains. Thus, the modulation of specific interactions between the alpha and beta subunit cytoplasmic domains may regulate transmembrane signaling through integrins. In addition, these activating mutations induce dominant alterations in cellular behavior, such as the assembly of the extracellular matrix. Consequently, somatic mutations in integrin cytoplasmic domains could have profound effects in vivo on integrin-dependent functions such as matrix assembly, cell migration, and anchorage-dependent cell growth and survival.</abstract><cop>United States</cop><pmid>8636068</pmid><doi>10.1074/jbc.271.12.6571</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1996-03, Vol.271 (12), p.6571-6574 |
| issn | 0021-9258 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_15599089 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Animals Cell Adhesion Molecules - metabolism Cricetinae DNA, Complementary Focal Adhesion Protein-Tyrosine Kinases Integrins - chemistry Integrins - genetics Integrins - metabolism Molecular Sequence Data Mutagenesis, Site-Directed Phosphorylation Point Mutation Protein Conformation Protein-Tyrosine Kinases - metabolism Signal Transduction |
| title | Breaking the integrin hinge. A defined structural constraint regulates integrin signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T09%3A01%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Breaking%20the%20integrin%20hinge.%20A%20defined%20structural%20constraint%20regulates%20integrin%20signaling&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Hughes,%20P%20E&rft.date=1996-03-22&rft.volume=271&rft.issue=12&rft.spage=6571&rft.epage=6574&rft.pages=6571-6574&rft.issn=0021-9258&rft_id=info:doi/10.1074/jbc.271.12.6571&rft_dat=%3Cproquest_pubme%3E15599089%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=15599089&rft_id=info:pmid/8636068&rfr_iscdi=true |