Discs Large (Dlg1) Complexes in Lymphocyte Activation
T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in resp...
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| Veröffentlicht in: | The Journal of cell biology 2004-07, Vol.166 (2), p.173-178 |
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| container_title | The Journal of cell biology |
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| creator | Xavier, Ramnik Rabizadeh, Shahrooz Ishiguro, Kazuhiro Andre, Niko Ortiz, J. Bernabe Wachtel, Heather Morris, David G. Lopez-Ilasaca, Marco Shaw, Albert C. Swat, Wojciech Seed, Brian |
| description | T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in response to activation remains poorly understood. We show here that in T cells Discs large (Dlg1), a PDZ domain-containing protein, is recruited upon activation to cortical actin and forms complexes with early participants in T cell activation. Transient overexpression of Dlg1 attenuates basal and Vav1-induced NFAT reporter activation. Reduction of Dlg1 expression by RNA interference enhances both CD3- and superantigen-mediated NFAT activation. Attenuation of antigen receptor signaling appears to be a complex, highly orchestrated event that involves the mutual segregation of important elements of the early signaling complex. |
| doi_str_mv | 10.1083/jcb.200309044 |
| format | Article |
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Bernabe ; Wachtel, Heather ; Morris, David G. ; Lopez-Ilasaca, Marco ; Shaw, Albert C. ; Swat, Wojciech ; Seed, Brian</creator><creatorcontrib>Xavier, Ramnik ; Rabizadeh, Shahrooz ; Ishiguro, Kazuhiro ; Andre, Niko ; Ortiz, J. Bernabe ; Wachtel, Heather ; Morris, David G. ; Lopez-Ilasaca, Marco ; Shaw, Albert C. ; Swat, Wojciech ; Seed, Brian</creatorcontrib><description>T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in response to activation remains poorly understood. We show here that in T cells Discs large (Dlg1), a PDZ domain-containing protein, is recruited upon activation to cortical actin and forms complexes with early participants in T cell activation. Transient overexpression of Dlg1 attenuates basal and Vav1-induced NFAT reporter activation. Reduction of Dlg1 expression by RNA interference enhances both CD3- and superantigen-mediated NFAT activation. Attenuation of antigen receptor signaling appears to be a complex, highly orchestrated event that involves the mutual segregation of important elements of the early signaling complex.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.200309044</identifier><identifier>PMID: 15263016</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Actins ; Actins - metabolism ; Adaptor Proteins, Signal Transducing ; Animals ; Antibodies ; Antigens ; B lymphocytes ; CD3 Complex - physiology ; Cell lines ; Cell membranes ; Cells ; Discs Large Homolog 1 Protein ; DNA-Binding Proteins - metabolism ; Drosophila ; Guanylate Kinases ; Humans ; Immune system ; Jurkat Cells ; Lymphocyte Activation ; Membrane Proteins ; Mice ; Mice, Transgenic ; Molecules ; NFATC Transcription Factors ; Nuclear Proteins ; Protein Transport ; Proteins ; Proteins - immunology ; Proteins - metabolism ; Rats ; Signal Transduction ; Signaling ; Superantigens - pharmacology ; T cell antigen receptors ; T lymphocytes ; T-Lymphocytes - chemistry ; T-Lymphocytes - metabolism ; T-Lymphocytes - physiology ; Transcription Factors - metabolism</subject><ispartof>The Journal of cell biology, 2004-07, Vol.166 (2), p.173-178</ispartof><rights>Copyright 2004 The Rockefeller University Press</rights><rights>Copyright The Rockerfeller University Press</rights><rights>Copyright Rockefeller University Press Jul 19, 2004</rights><rights>Copyright © 2004, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c394t-140dcf17c8fd76d3381eaf19d559a22f47b3793c1449b72b58d32356478eb3793</citedby><cites>FETCH-LOGICAL-c394t-140dcf17c8fd76d3381eaf19d559a22f47b3793c1449b72b58d32356478eb3793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15263016$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xavier, Ramnik</creatorcontrib><creatorcontrib>Rabizadeh, Shahrooz</creatorcontrib><creatorcontrib>Ishiguro, Kazuhiro</creatorcontrib><creatorcontrib>Andre, Niko</creatorcontrib><creatorcontrib>Ortiz, J. Bernabe</creatorcontrib><creatorcontrib>Wachtel, Heather</creatorcontrib><creatorcontrib>Morris, David G.</creatorcontrib><creatorcontrib>Lopez-Ilasaca, Marco</creatorcontrib><creatorcontrib>Shaw, Albert C.</creatorcontrib><creatorcontrib>Swat, Wojciech</creatorcontrib><creatorcontrib>Seed, Brian</creatorcontrib><title>Discs Large (Dlg1) Complexes in Lymphocyte Activation</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in response to activation remains poorly understood. We show here that in T cells Discs large (Dlg1), a PDZ domain-containing protein, is recruited upon activation to cortical actin and forms complexes with early participants in T cell activation. Transient overexpression of Dlg1 attenuates basal and Vav1-induced NFAT reporter activation. Reduction of Dlg1 expression by RNA interference enhances both CD3- and superantigen-mediated NFAT activation. Attenuation of antigen receptor signaling appears to be a complex, highly orchestrated event that involves the mutual segregation of important elements of the early signaling complex.</description><subject>Actins</subject><subject>Actins - metabolism</subject><subject>Adaptor Proteins, Signal Transducing</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>B lymphocytes</subject><subject>CD3 Complex - physiology</subject><subject>Cell lines</subject><subject>Cell membranes</subject><subject>Cells</subject><subject>Discs Large Homolog 1 Protein</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drosophila</subject><subject>Guanylate Kinases</subject><subject>Humans</subject><subject>Immune system</subject><subject>Jurkat Cells</subject><subject>Lymphocyte Activation</subject><subject>Membrane Proteins</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecules</subject><subject>NFATC Transcription Factors</subject><subject>Nuclear Proteins</subject><subject>Protein Transport</subject><subject>Proteins</subject><subject>Proteins - immunology</subject><subject>Proteins - metabolism</subject><subject>Rats</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Superantigens - pharmacology</subject><subject>T cell antigen receptors</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes - chemistry</subject><subject>T-Lymphocytes - metabolism</subject><subject>T-Lymphocytes - physiology</subject><subject>Transcription Factors - metabolism</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1P20AQxVcVqATaY28IWRxQOZjO7Kf3goRCC0iRemnPq_V6HRzZ3nTXich_j9NEUHrhNIf305s38wj5gnCFULBvC1deUQAGGjj_QCYoOOQFcjggEwCKuRZUHJHjlBYAwBVnH8kRCioZoJwQcdskl7KZjXOffb1t53iZTUO3bP2TT1nTZ7NNt3wMbjP47MYNzdoOTeg_kcPatsl_3s8T8vvH91_T-3z28-5hejPLHdN8yMcUlatRuaKulKwYK9DbGnUlhLaU1lyVTGnmkHNdKlqKomKUCclV4f8qJ-R657tclZ2vnO-HaFuzjE1n48YE25i3St88mnlYG4qKMlCjwcXeIIY_K58G0433-ra1vQ-rZKRUlBco3gVRaV1IvQXP_wMXYRX78QvbpaARlByhfAe5GFKKvn6JjGC2tZmxNvNS28if_XvnK73vaQROd8AiDSG-6pJS0JQ9A7P6mhQ</recordid><startdate>20040719</startdate><enddate>20040719</enddate><creator>Xavier, Ramnik</creator><creator>Rabizadeh, Shahrooz</creator><creator>Ishiguro, Kazuhiro</creator><creator>Andre, Niko</creator><creator>Ortiz, J. 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| subjects | Actins Actins - metabolism Adaptor Proteins, Signal Transducing Animals Antibodies Antigens B lymphocytes CD3 Complex - physiology Cell lines Cell membranes Cells Discs Large Homolog 1 Protein DNA-Binding Proteins - metabolism Drosophila Guanylate Kinases Humans Immune system Jurkat Cells Lymphocyte Activation Membrane Proteins Mice Mice, Transgenic Molecules NFATC Transcription Factors Nuclear Proteins Protein Transport Proteins Proteins - immunology Proteins - metabolism Rats Signal Transduction Signaling Superantigens - pharmacology T cell antigen receptors T lymphocytes T-Lymphocytes - chemistry T-Lymphocytes - metabolism T-Lymphocytes - physiology Transcription Factors - metabolism |
| title | Discs Large (Dlg1) Complexes in Lymphocyte Activation |
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