Cutting Edge: A Role for the Adaptor Protein LAT in Human NK Cell-Mediated Cytotoxicity
Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effectors. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we describe a key role for the LAT (p36) adaptor prot...
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| Veröffentlicht in: | The Journal of immunology (1950) 1999-03, Vol.162 (5), p.2453-2456 |
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| container_end_page | 2456 |
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| container_issue | 5 |
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| container_title | The Journal of immunology (1950) |
| container_volume | 162 |
| creator | Jevremovic, Dragan Billadeau, Daniel D Schoon, Renee A Dick, Christopher J Irvin, Brenda J Zhang, Weiguo Samelson, Lawrence E Abraham, Robert T Leibson, Paul J |
| description | Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effectors. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we describe a key role for the LAT (p36) adaptor protein in human NK cell activation. LAT is tyrosine phosphorylated upon stimulation of NK cells through FcgammaRIII receptors and following direct contact with NK-sensitive target cells. This NK stimulation induces the association of LAT with several phosphotyrosine-containing proteins. In addition to the biochemical evidence showing LAT involvement in NK cell activation, a genetic model shows that LAT is required for FcR-dependent phosphorylation of phospholipase C-gamma. Furthermore, overexpression of LAT in NK cells leads to increased Ab-dependent cell-mediated cytotoxicity and "natural cytotoxicity," thus demonstrating a functional role for LAT in NK cells. These data suggest that LAT is an important adaptor protein for the regulation of human NK cell-mediated cytotoxicity. |
| doi_str_mv | 10.4049/jimmunol.162.5.2453 |
| format | Article |
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These data suggest that LAT is an important adaptor protein for the regulation of human NK cell-mediated cytotoxicity.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.162.5.2453</identifier><identifier>PMID: 10072481</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Adaptor Proteins, Signal Transducing ; Carrier Proteins - physiology ; Cell Line ; Cytotoxicity, Immunologic ; Humans ; Killer Cells, Natural - immunology ; Lymphocyte Activation ; Membrane Proteins ; Phosphoproteins - physiology ; Type C Phospholipases - physiology</subject><ispartof>The Journal of immunology (1950), 1999-03, Vol.162 (5), p.2453-2456</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-dc4f287d154c0dabbff84e3458cdc6ffbe78c90e3acef2c6360df1b424c23c203</citedby><cites>FETCH-LOGICAL-c378t-dc4f287d154c0dabbff84e3458cdc6ffbe78c90e3acef2c6360df1b424c23c203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10072481$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jevremovic, Dragan</creatorcontrib><creatorcontrib>Billadeau, Daniel D</creatorcontrib><creatorcontrib>Schoon, Renee A</creatorcontrib><creatorcontrib>Dick, Christopher J</creatorcontrib><creatorcontrib>Irvin, Brenda J</creatorcontrib><creatorcontrib>Zhang, Weiguo</creatorcontrib><creatorcontrib>Samelson, Lawrence E</creatorcontrib><creatorcontrib>Abraham, Robert T</creatorcontrib><creatorcontrib>Leibson, Paul J</creatorcontrib><title>Cutting Edge: A Role for the Adaptor Protein LAT in Human NK Cell-Mediated Cytotoxicity</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effectors. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we describe a key role for the LAT (p36) adaptor protein in human NK cell activation. LAT is tyrosine phosphorylated upon stimulation of NK cells through FcgammaRIII receptors and following direct contact with NK-sensitive target cells. This NK stimulation induces the association of LAT with several phosphotyrosine-containing proteins. In addition to the biochemical evidence showing LAT involvement in NK cell activation, a genetic model shows that LAT is required for FcR-dependent phosphorylation of phospholipase C-gamma. Furthermore, overexpression of LAT in NK cells leads to increased Ab-dependent cell-mediated cytotoxicity and "natural cytotoxicity," thus demonstrating a functional role for LAT in NK cells. These data suggest that LAT is an important adaptor protein for the regulation of human NK cell-mediated cytotoxicity.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Carrier Proteins - physiology</subject><subject>Cell Line</subject><subject>Cytotoxicity, Immunologic</subject><subject>Humans</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lymphocyte Activation</subject><subject>Membrane Proteins</subject><subject>Phosphoproteins - physiology</subject><subject>Type C Phospholipases - physiology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1P3DAURS3UCoaPX4BUedWuMn12HCfT3SiigBhohai6tBz7ecYoiaexo-n8e4IGJFb3Lc69ejqEXDKYCxCL78--68Y-tHMm-byYc1HkR2TGigIyKUF-IjMAzjNWyvKEnMb4DAASuDgmJwyg5KJiM_K3HlPy_Zpe2TX-oEv6GFqkLgw0bZAurd6m6f49hIS-p6vlE53iZux0Tx_uaI1tm92j9TqhpfU-hRT-e-PT_px8drqNePGWZ-TPz6un-iZb_bq-rZerzORllTJrhONVaVkhDFjdNM5VAnNRVMYa6VyDZWUWgLk26LiRuQTrWCO4MDw3HPIz8vWwux3CvxFjUp2PZnpL9xjGqORCshLkYgLzA2iGEOOATm0H3-lhrxioV5_q3aeafKpCvfqcWl_e5semQ_uhcxA4Ad8OwMavNzs_oIqdbtsJZ2q3232YegGMaYDS</recordid><startdate>19990301</startdate><enddate>19990301</enddate><creator>Jevremovic, Dragan</creator><creator>Billadeau, Daniel D</creator><creator>Schoon, Renee A</creator><creator>Dick, Christopher J</creator><creator>Irvin, Brenda J</creator><creator>Zhang, Weiguo</creator><creator>Samelson, Lawrence E</creator><creator>Abraham, Robert T</creator><creator>Leibson, Paul J</creator><general>Am Assoc Immnol</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>7X8</scope></search><sort><creationdate>19990301</creationdate><title>Cutting Edge: A Role for the Adaptor Protein LAT in Human NK Cell-Mediated Cytotoxicity</title><author>Jevremovic, Dragan ; Billadeau, Daniel D ; Schoon, Renee A ; Dick, Christopher J ; Irvin, Brenda J ; Zhang, Weiguo ; Samelson, Lawrence E ; Abraham, Robert T ; Leibson, Paul J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-dc4f287d154c0dabbff84e3458cdc6ffbe78c90e3acef2c6360df1b424c23c203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Carrier Proteins - physiology</topic><topic>Cell Line</topic><topic>Cytotoxicity, Immunologic</topic><topic>Humans</topic><topic>Killer Cells, Natural - immunology</topic><topic>Lymphocyte Activation</topic><topic>Membrane Proteins</topic><topic>Phosphoproteins - physiology</topic><topic>Type C Phospholipases - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jevremovic, Dragan</creatorcontrib><creatorcontrib>Billadeau, Daniel D</creatorcontrib><creatorcontrib>Schoon, Renee A</creatorcontrib><creatorcontrib>Dick, Christopher J</creatorcontrib><creatorcontrib>Irvin, Brenda J</creatorcontrib><creatorcontrib>Zhang, Weiguo</creatorcontrib><creatorcontrib>Samelson, Lawrence E</creatorcontrib><creatorcontrib>Abraham, Robert T</creatorcontrib><creatorcontrib>Leibson, Paul J</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>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jevremovic, Dragan</au><au>Billadeau, Daniel D</au><au>Schoon, Renee A</au><au>Dick, Christopher J</au><au>Irvin, Brenda J</au><au>Zhang, Weiguo</au><au>Samelson, Lawrence E</au><au>Abraham, Robert T</au><au>Leibson, Paul J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cutting Edge: A Role for the Adaptor Protein LAT in Human NK Cell-Mediated Cytotoxicity</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1999-03-01</date><risdate>1999</risdate><volume>162</volume><issue>5</issue><spage>2453</spage><epage>2456</epage><pages>2453-2456</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effectors. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we describe a key role for the LAT (p36) adaptor protein in human NK cell activation. LAT is tyrosine phosphorylated upon stimulation of NK cells through FcgammaRIII receptors and following direct contact with NK-sensitive target cells. This NK stimulation induces the association of LAT with several phosphotyrosine-containing proteins. In addition to the biochemical evidence showing LAT involvement in NK cell activation, a genetic model shows that LAT is required for FcR-dependent phosphorylation of phospholipase C-gamma. Furthermore, overexpression of LAT in NK cells leads to increased Ab-dependent cell-mediated cytotoxicity and "natural cytotoxicity," thus demonstrating a functional role for LAT in NK cells. These data suggest that LAT is an important adaptor protein for the regulation of human NK cell-mediated cytotoxicity.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>10072481</pmid><doi>10.4049/jimmunol.162.5.2453</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adaptor Proteins, Signal Transducing Carrier Proteins - physiology Cell Line Cytotoxicity, Immunologic Humans Killer Cells, Natural - immunology Lymphocyte Activation Membrane Proteins Phosphoproteins - physiology Type C Phospholipases - physiology |
| title | Cutting Edge: A Role for the Adaptor Protein LAT in Human NK Cell-Mediated Cytotoxicity |
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