Evidence for a p21(ras)/Raf-1/MEK-1/ERK-2-independent pathway in stimulation of IL-2 gene transcription in human primary T lymphocytes
T cell stimulation leads to triggering of signals transmitted from the cell membrane to the nucleus through TCR/CD3 proteins. Characterization of these signals largely results from the use of cell lines stimulated with anti-CD3 monoclonal antibodies. These studies have established that activation ca...
Gespeichert in:
Veröffentlicht in: | The Journal of biological chemistry 1999-09, Vol.274 (36), p.25743-25748 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 25748 |
---|---|
container_issue | 36 |
container_start_page | 25743 |
container_title | The Journal of biological chemistry |
container_volume | 274 |
creator | Lafont, V Ottones, F Liautard, J Favero, J |
description | T cell stimulation leads to triggering of signals transmitted from the cell membrane to the nucleus through TCR/CD3 proteins. Characterization of these signals largely results from the use of cell lines stimulated with anti-CD3 monoclonal antibodies. These studies have established that activation caused a rapid increase in the formation of GTP-bound Ras, which stimulates the mitogen-activated protein kinase pathway involving the extracellular-regulated kinase-2 (ERK-2) and activates the nuclear factor of activated T cells (NF-AT) that regulates interleukin-2 (IL-2) gene transcription. In the present study, we used human primary T cells, and we investigated the intracellular signals triggered by two different anti-CD3 monoclonal antibodies (UCHT1 and X-35), which both strongly induce cell proliferation. We found that, in contrast to the commonly used UCHT1, X-35 activated IL-2 gene transcription without stimulation of the Raf-1/mitogen-activated ERK kinase-1 (MEK-1)/ERK-2 phosphorylation cascade; we also showed that X-35 stimulation, which triggers an ERK-2-independent pathway, does not involve activation of p21(ras). In addition to demonstrating that activation of p21(ras) and of its Raf-1/MEK-1/ERK-2 effector pathway is not an event obligatorily triggered upon TCR/CD3 ligation, these results provide the first evidence of the existence of a p21(ras)/ERK-2-independent pathway for IL-2 gene transcription in human primary T lymphocytes. |
doi_str_mv | 10.1074/jbc.274.36.25743 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69994073</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69994073</sourcerecordid><originalsourceid>FETCH-LOGICAL-c337t-1c72fbbe743f88849ce041f22de3cf0d3b53844812af16a668cb6df5898f50d33</originalsourceid><addsrcrecordid>eNpNkD9PwzAQxT2AaCnsTMgTgiGt_yVxRlQFqFqEVJXZchybpkqcYCegfgE-Ny7twA13w733dPcD4AajKUYpm-0KNSUpm9JkSuKU0TMwRojgKCMxH4FL73coFMvwBRhhxBJGMRmDn_yrKrVVGprWQQk7gu-d9A-ztTQRnr3my9Dz9TIiUWVL3enQbA872W-_5R5WFvq-aoZa9lVrYWvgYhUR-KGthr2T1itXdX-roNwOjbSwc1Uj3R5uYL1vum2r9r32V-DcyNrr69OcgPenfDN_iVZvz4v54ypSlKZ9hFVKTFHo8J7hnLNMacSwIaTUVBlU0iKmnDGOiTQ4kUnCVZGUJuYZN3FY0wm4O-Z2rv0ctO9FU3ml61pa3Q5eJFmWMZQehOgoVK713mkjTncLjMSBtwi8ReAtaCL-eAfL7Sl7KBpd_jMcYdNfhB19ZQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69994073</pqid></control><display><type>article</type><title>Evidence for a p21(ras)/Raf-1/MEK-1/ERK-2-independent pathway in stimulation of IL-2 gene transcription in human primary T lymphocytes</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Lafont, V ; Ottones, F ; Liautard, J ; Favero, J</creator><creatorcontrib>Lafont, V ; Ottones, F ; Liautard, J ; Favero, J</creatorcontrib><description>T cell stimulation leads to triggering of signals transmitted from the cell membrane to the nucleus through TCR/CD3 proteins. Characterization of these signals largely results from the use of cell lines stimulated with anti-CD3 monoclonal antibodies. These studies have established that activation caused a rapid increase in the formation of GTP-bound Ras, which stimulates the mitogen-activated protein kinase pathway involving the extracellular-regulated kinase-2 (ERK-2) and activates the nuclear factor of activated T cells (NF-AT) that regulates interleukin-2 (IL-2) gene transcription. In the present study, we used human primary T cells, and we investigated the intracellular signals triggered by two different anti-CD3 monoclonal antibodies (UCHT1 and X-35), which both strongly induce cell proliferation. We found that, in contrast to the commonly used UCHT1, X-35 activated IL-2 gene transcription without stimulation of the Raf-1/mitogen-activated ERK kinase-1 (MEK-1)/ERK-2 phosphorylation cascade; we also showed that X-35 stimulation, which triggers an ERK-2-independent pathway, does not involve activation of p21(ras). In addition to demonstrating that activation of p21(ras) and of its Raf-1/MEK-1/ERK-2 effector pathway is not an event obligatorily triggered upon TCR/CD3 ligation, these results provide the first evidence of the existence of a p21(ras)/ERK-2-independent pathway for IL-2 gene transcription in human primary T lymphocytes.</description><identifier>ISSN: 0021-9258</identifier><identifier>DOI: 10.1074/jbc.274.36.25743</identifier><identifier>PMID: 10464312</identifier><language>eng</language><publisher>United States</publisher><subject>Cells, Cultured ; Humans ; Interleukin-1 - biosynthesis ; Interleukin-1 - genetics ; Lymphocyte Activation ; Mitogen-Activated Protein Kinase 1 - genetics ; Mitogen-Activated Protein Kinase 1 - metabolism ; Proto-Oncogene Proteins c-raf - genetics ; Proto-Oncogene Proteins c-raf - metabolism ; Proto-Oncogene Proteins p21(ras) - genetics ; Proto-Oncogene Proteins p21(ras) - metabolism ; Signal Transduction - genetics ; Signal Transduction - immunology ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Transcription, Genetic</subject><ispartof>The Journal of biological chemistry, 1999-09, Vol.274 (36), p.25743-25748</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-1c72fbbe743f88849ce041f22de3cf0d3b53844812af16a668cb6df5898f50d33</citedby><cites>FETCH-LOGICAL-c337t-1c72fbbe743f88849ce041f22de3cf0d3b53844812af16a668cb6df5898f50d33</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/10464312$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lafont, V</creatorcontrib><creatorcontrib>Ottones, F</creatorcontrib><creatorcontrib>Liautard, J</creatorcontrib><creatorcontrib>Favero, J</creatorcontrib><title>Evidence for a p21(ras)/Raf-1/MEK-1/ERK-2-independent pathway in stimulation of IL-2 gene transcription in human primary T lymphocytes</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>T cell stimulation leads to triggering of signals transmitted from the cell membrane to the nucleus through TCR/CD3 proteins. Characterization of these signals largely results from the use of cell lines stimulated with anti-CD3 monoclonal antibodies. These studies have established that activation caused a rapid increase in the formation of GTP-bound Ras, which stimulates the mitogen-activated protein kinase pathway involving the extracellular-regulated kinase-2 (ERK-2) and activates the nuclear factor of activated T cells (NF-AT) that regulates interleukin-2 (IL-2) gene transcription. In the present study, we used human primary T cells, and we investigated the intracellular signals triggered by two different anti-CD3 monoclonal antibodies (UCHT1 and X-35), which both strongly induce cell proliferation. We found that, in contrast to the commonly used UCHT1, X-35 activated IL-2 gene transcription without stimulation of the Raf-1/mitogen-activated ERK kinase-1 (MEK-1)/ERK-2 phosphorylation cascade; we also showed that X-35 stimulation, which triggers an ERK-2-independent pathway, does not involve activation of p21(ras). In addition to demonstrating that activation of p21(ras) and of its Raf-1/MEK-1/ERK-2 effector pathway is not an event obligatorily triggered upon TCR/CD3 ligation, these results provide the first evidence of the existence of a p21(ras)/ERK-2-independent pathway for IL-2 gene transcription in human primary T lymphocytes.</description><subject>Cells, Cultured</subject><subject>Humans</subject><subject>Interleukin-1 - biosynthesis</subject><subject>Interleukin-1 - genetics</subject><subject>Lymphocyte Activation</subject><subject>Mitogen-Activated Protein Kinase 1 - genetics</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Proto-Oncogene Proteins c-raf - genetics</subject><subject>Proto-Oncogene Proteins c-raf - metabolism</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Proto-Oncogene Proteins p21(ras) - metabolism</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - immunology</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Transcription, Genetic</subject><issn>0021-9258</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkD9PwzAQxT2AaCnsTMgTgiGt_yVxRlQFqFqEVJXZchybpkqcYCegfgE-Ny7twA13w733dPcD4AajKUYpm-0KNSUpm9JkSuKU0TMwRojgKCMxH4FL73coFMvwBRhhxBJGMRmDn_yrKrVVGprWQQk7gu-d9A-ztTQRnr3my9Dz9TIiUWVL3enQbA872W-_5R5WFvq-aoZa9lVrYWvgYhUR-KGthr2T1itXdX-roNwOjbSwc1Uj3R5uYL1vum2r9r32V-DcyNrr69OcgPenfDN_iVZvz4v54ypSlKZ9hFVKTFHo8J7hnLNMacSwIaTUVBlU0iKmnDGOiTQ4kUnCVZGUJuYZN3FY0wm4O-Z2rv0ctO9FU3ml61pa3Q5eJFmWMZQehOgoVK713mkjTncLjMSBtwi8ReAtaCL-eAfL7Sl7KBpd_jMcYdNfhB19ZQ</recordid><startdate>19990903</startdate><enddate>19990903</enddate><creator>Lafont, V</creator><creator>Ottones, F</creator><creator>Liautard, J</creator><creator>Favero, J</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>19990903</creationdate><title>Evidence for a p21(ras)/Raf-1/MEK-1/ERK-2-independent pathway in stimulation of IL-2 gene transcription in human primary T lymphocytes</title><author>Lafont, V ; Ottones, F ; Liautard, J ; Favero, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-1c72fbbe743f88849ce041f22de3cf0d3b53844812af16a668cb6df5898f50d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Cells, Cultured</topic><topic>Humans</topic><topic>Interleukin-1 - biosynthesis</topic><topic>Interleukin-1 - genetics</topic><topic>Lymphocyte Activation</topic><topic>Mitogen-Activated Protein Kinase 1 - genetics</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Proto-Oncogene Proteins c-raf - genetics</topic><topic>Proto-Oncogene Proteins c-raf - metabolism</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Proto-Oncogene Proteins p21(ras) - metabolism</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - immunology</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lafont, V</creatorcontrib><creatorcontrib>Ottones, F</creatorcontrib><creatorcontrib>Liautard, J</creatorcontrib><creatorcontrib>Favero, 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 biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lafont, V</au><au>Ottones, F</au><au>Liautard, J</au><au>Favero, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence for a p21(ras)/Raf-1/MEK-1/ERK-2-independent pathway in stimulation of IL-2 gene transcription in human primary T lymphocytes</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1999-09-03</date><risdate>1999</risdate><volume>274</volume><issue>36</issue><spage>25743</spage><epage>25748</epage><pages>25743-25748</pages><issn>0021-9258</issn><abstract>T cell stimulation leads to triggering of signals transmitted from the cell membrane to the nucleus through TCR/CD3 proteins. Characterization of these signals largely results from the use of cell lines stimulated with anti-CD3 monoclonal antibodies. These studies have established that activation caused a rapid increase in the formation of GTP-bound Ras, which stimulates the mitogen-activated protein kinase pathway involving the extracellular-regulated kinase-2 (ERK-2) and activates the nuclear factor of activated T cells (NF-AT) that regulates interleukin-2 (IL-2) gene transcription. In the present study, we used human primary T cells, and we investigated the intracellular signals triggered by two different anti-CD3 monoclonal antibodies (UCHT1 and X-35), which both strongly induce cell proliferation. We found that, in contrast to the commonly used UCHT1, X-35 activated IL-2 gene transcription without stimulation of the Raf-1/mitogen-activated ERK kinase-1 (MEK-1)/ERK-2 phosphorylation cascade; we also showed that X-35 stimulation, which triggers an ERK-2-independent pathway, does not involve activation of p21(ras). In addition to demonstrating that activation of p21(ras) and of its Raf-1/MEK-1/ERK-2 effector pathway is not an event obligatorily triggered upon TCR/CD3 ligation, these results provide the first evidence of the existence of a p21(ras)/ERK-2-independent pathway for IL-2 gene transcription in human primary T lymphocytes.</abstract><cop>United States</cop><pmid>10464312</pmid><doi>10.1074/jbc.274.36.25743</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0021-9258 |
ispartof | The Journal of biological chemistry, 1999-09, Vol.274 (36), p.25743-25748 |
issn | 0021-9258 |
language | eng |
recordid | cdi_proquest_miscellaneous_69994073 |
source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
subjects | Cells, Cultured Humans Interleukin-1 - biosynthesis Interleukin-1 - genetics Lymphocyte Activation Mitogen-Activated Protein Kinase 1 - genetics Mitogen-Activated Protein Kinase 1 - metabolism Proto-Oncogene Proteins c-raf - genetics Proto-Oncogene Proteins c-raf - metabolism Proto-Oncogene Proteins p21(ras) - genetics Proto-Oncogene Proteins p21(ras) - metabolism Signal Transduction - genetics Signal Transduction - immunology T-Lymphocytes - immunology T-Lymphocytes - metabolism Transcription, Genetic |
title | Evidence for a p21(ras)/Raf-1/MEK-1/ERK-2-independent pathway in stimulation of IL-2 gene transcription in human primary T lymphocytes |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T17%3A52%3A49IST&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=Evidence%20for%20a%20p21(ras)/Raf-1/MEK-1/ERK-2-independent%20pathway%20in%20stimulation%20of%20IL-2%20gene%20transcription%20in%20human%20primary%20T%20lymphocytes&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Lafont,%20V&rft.date=1999-09-03&rft.volume=274&rft.issue=36&rft.spage=25743&rft.epage=25748&rft.pages=25743-25748&rft.issn=0021-9258&rft_id=info:doi/10.1074/jbc.274.36.25743&rft_dat=%3Cproquest_cross%3E69994073%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=69994073&rft_id=info:pmid/10464312&rfr_iscdi=true |