Molecular Editing of Cellular Responses by the High-Affinity Receptor for IgE
Cellular responses elicited by cell surface receptors differ according to stimulus strength. We investigated how the high-affinity receptor for immunoglobulin E (IgE) modulates the response of mast cells to a high- or low-affinity stimulus. Both high- and low-affinity stimuli elicited similar recept...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2014-02, Vol.343 (6174), p.1021-1025 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Suzuki, Ryo Leach, Sarah Liu, Wenhua Ralston, Evelyn Scheffel, Jörg Zhang, Weiguo Lowell, Clifford A. Rivera, Juan |
| description | Cellular responses elicited by cell surface receptors differ according to stimulus strength. We investigated how the high-affinity receptor for immunoglobulin E (IgE) modulates the response of mast cells to a high- or low-affinity stimulus. Both high- and low-affinity stimuli elicited similar receptor phosphorylation; however, differences were observed in receptor cluster size, mobility, distribution, and the cells' effector responses. Low-affinity stimulation increased receptor association with the Src family kinase Fgr and shifted signals from the adapter LAT1 to the related adapter LAT2. LAT1-dependent calcium signals required for mast cell degranulation were dampened, but the role of LAT2 in chemokine production was enhanced, altering immune cell recruitment at the site of inflammation. These findings uncover how receptor discrimination of stimulus strength can be interpreted as distinct in vivo outcomes. |
| doi_str_mv | 10.1126/science.1246976 |
| format | Article |
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We investigated how the high-affinity receptor for immunoglobulin E (IgE) modulates the response of mast cells to a high- or low-affinity stimulus. Both high- and low-affinity stimuli elicited similar receptor phosphorylation; however, differences were observed in receptor cluster size, mobility, distribution, and the cells' effector responses. Low-affinity stimulation increased receptor association with the Src family kinase Fgr and shifted signals from the adapter LAT1 to the related adapter LAT2. LAT1-dependent calcium signals required for mast cell degranulation were dampened, but the role of LAT2 in chemokine production was enhanced, altering immune cell recruitment at the site of inflammation. These findings uncover how receptor discrimination of stimulus strength can be interpreted as distinct in vivo outcomes.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1246976</identifier><identifier>PMID: 24505132</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Adaptor Proteins, Signal Transducing - metabolism ; Allergies ; Amino Acid Transport System y+ - metabolism ; Animals ; Antibodies ; Antigens ; Auxins ; Calcium ; Cattle ; Cell Movement ; Cellular biology ; Chemokines - metabolism ; Dinitrophenols ; Fluorescence ; Fusion Regulatory Protein 1, Light Chains - metabolism ; Immunoglobulin E - metabolism ; Immunoglobulins ; Inflammation - immunology ; Mast cells ; Mast Cells - immunology ; Membrane Proteins - metabolism ; Mice ; Neutrophils ; Phosphoproteins - metabolism ; Phosphorylation ; Proto-Oncogene Proteins - metabolism ; Receptors ; Receptors, IgE - metabolism ; src-Family Kinases - metabolism ; T tests</subject><ispartof>Science (American Association for the Advancement of Science), 2014-02, Vol.343 (6174), p.1021-1025</ispartof><rights>Copyright © 2014 American Association for the Advancement of Science</rights><rights>Copyright © 2014, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-3e29c8dda6d4e873aa482dc0e11491f3289304fa4c33941da20d8e264302ed113</citedby><cites>FETCH-LOGICAL-c509t-3e29c8dda6d4e873aa482dc0e11491f3289304fa4c33941da20d8e264302ed113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24743379$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24743379$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24505132$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suzuki, Ryo</creatorcontrib><creatorcontrib>Leach, Sarah</creatorcontrib><creatorcontrib>Liu, Wenhua</creatorcontrib><creatorcontrib>Ralston, Evelyn</creatorcontrib><creatorcontrib>Scheffel, Jörg</creatorcontrib><creatorcontrib>Zhang, Weiguo</creatorcontrib><creatorcontrib>Lowell, Clifford A.</creatorcontrib><creatorcontrib>Rivera, Juan</creatorcontrib><title>Molecular Editing of Cellular Responses by the High-Affinity Receptor for IgE</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Cellular responses elicited by cell surface receptors differ according to stimulus strength. We investigated how the high-affinity receptor for immunoglobulin E (IgE) modulates the response of mast cells to a high- or low-affinity stimulus. Both high- and low-affinity stimuli elicited similar receptor phosphorylation; however, differences were observed in receptor cluster size, mobility, distribution, and the cells' effector responses. Low-affinity stimulation increased receptor association with the Src family kinase Fgr and shifted signals from the adapter LAT1 to the related adapter LAT2. LAT1-dependent calcium signals required for mast cell degranulation were dampened, but the role of LAT2 in chemokine production was enhanced, altering immune cell recruitment at the site of inflammation. 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metabolism</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Receptors</subject><subject>Receptors, IgE - metabolism</subject><subject>src-Family Kinases - metabolism</subject><subject>T tests</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1rGzEUxEVpaNy0555aFnLpZZOnr13pUgjGbQIJhdKehSK9tWXWK1faDfi_jxy7IQ1CCDQ_DW80hHyicEEpay6zCzg4vKBMNLpt3pAZBS1rzYC_JTMA3tQKWnlK3ue8Biia5u_IKRMSJOVsRu7uYo9u6m2qFj6MYVhWsavm2PdPd78wb-OQMVf3u2pcYXUdlqv6quvCEMZdkR1ux5iqruyb5eIDOelsn_Hj8Twjf74vfs-v69ufP27mV7e1k6DHmiPTTnlvGy9QtdxaoZh3gJQKTTvOlOYgOisc51pQbxl4hawRHBh6SvkZ-Xbw3U73G_QOhzHZ3mxT2Ni0M9EG878yhJVZxgcjqFIS2mLw9WiQ4t8J82g2IbuS2g4Yp2yoBC4l440q6PkrdB2nNJR4T9R-if1ElwfKpZhzwu55GApmX5U5VmWOVZUXX15meOb_dVOAzwdgncsXv9BbwXmr-SNsQpl-</recordid><startdate>20140228</startdate><enddate>20140228</enddate><creator>Suzuki, Ryo</creator><creator>Leach, Sarah</creator><creator>Liu, Wenhua</creator><creator>Ralston, Evelyn</creator><creator>Scheffel, Jörg</creator><creator>Zhang, Weiguo</creator><creator>Lowell, Clifford A.</creator><creator>Rivera, Juan</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140228</creationdate><title>Molecular Editing of Cellular Responses by the High-Affinity Receptor for IgE</title><author>Suzuki, Ryo ; Leach, Sarah ; Liu, Wenhua ; Ralston, Evelyn ; Scheffel, Jörg ; Zhang, Weiguo ; Lowell, Clifford A. ; Rivera, Juan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-3e29c8dda6d4e873aa482dc0e11491f3289304fa4c33941da20d8e264302ed113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adaptor Proteins, Signal Transducing - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suzuki, Ryo</au><au>Leach, Sarah</au><au>Liu, Wenhua</au><au>Ralston, Evelyn</au><au>Scheffel, Jörg</au><au>Zhang, Weiguo</au><au>Lowell, Clifford A.</au><au>Rivera, Juan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Editing of Cellular Responses by the High-Affinity Receptor for IgE</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2014-02-28</date><risdate>2014</risdate><volume>343</volume><issue>6174</issue><spage>1021</spage><epage>1025</epage><pages>1021-1025</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Cellular responses elicited by cell surface receptors differ according to stimulus strength. We investigated how the high-affinity receptor for immunoglobulin E (IgE) modulates the response of mast cells to a high- or low-affinity stimulus. Both high- and low-affinity stimuli elicited similar receptor phosphorylation; however, differences were observed in receptor cluster size, mobility, distribution, and the cells' effector responses. Low-affinity stimulation increased receptor association with the Src family kinase Fgr and shifted signals from the adapter LAT1 to the related adapter LAT2. LAT1-dependent calcium signals required for mast cell degranulation were dampened, but the role of LAT2 in chemokine production was enhanced, altering immune cell recruitment at the site of inflammation. These findings uncover how receptor discrimination of stimulus strength can be interpreted as distinct in vivo outcomes.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>24505132</pmid><doi>10.1126/science.1246976</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Science Magazine; JSTOR Archive Collection A-Z Listing |
| subjects | Adaptor Proteins, Signal Transducing - metabolism Allergies Amino Acid Transport System y+ - metabolism Animals Antibodies Antigens Auxins Calcium Cattle Cell Movement Cellular biology Chemokines - metabolism Dinitrophenols Fluorescence Fusion Regulatory Protein 1, Light Chains - metabolism Immunoglobulin E - metabolism Immunoglobulins Inflammation - immunology Mast cells Mast Cells - immunology Membrane Proteins - metabolism Mice Neutrophils Phosphoproteins - metabolism Phosphorylation Proto-Oncogene Proteins - metabolism Receptors Receptors, IgE - metabolism src-Family Kinases - metabolism T tests |
| title | Molecular Editing of Cellular Responses by the High-Affinity Receptor for IgE |
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