Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling
THE interaction of interleukin-2 (IL-2) and IL-2 receptors criti-cally regulates the T-cell immune response following antigen activation 1,2 . IL-2 can signal through high or intermediate affinity receptors which contain IL-2Rα (refs 3, 4) + β (refs5–8) + γ (ref. 9) or β + γ chains, respectively. IL...
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| Veröffentlicht in: | Nature (London) 1994-05, Vol.369 (6478), p.330-333 |
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| creator | Nakamura, Yoshlaki Russell, Sarah M. Mess, Sarah A. Friedmann, Michael Erdos, Michael Francois, Christine Jacques, Yannick Adelstein, Stephen Leonard, Warren J. |
| description | THE interaction of interleukin-2 (IL-2) and IL-2 receptors criti-cally regulates the T-cell immune response following antigen activation
1,2
. IL-2 can signal through high or intermediate affinity receptors which contain IL-2Rα (refs 3, 4) + β (refs5–8) + γ (ref. 9) or β + γ chains, respectively. IL-2Rγ is a common γ chain, γ
c
, also shared by the IL-7 (ref. 10) and IL-4 (refs 11,12) receptors, which when mutated results in X-linked severe combined immunodeficiency
13
. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the β- and γ
c
-chain cytoplasmic domains. Anti-I L-2Rα monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracel-lular domains of IL-2Rβ and γ
c
are replaced by that of IL-2Rα. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2Rα and that the β-transmembrane domain is not required for receptor chain inter-actions. Finally, we provide a method for mapping residues in the γ
c
cytoplasmic domain even in cells that constitutively express γ
c
. |
| doi_str_mv | 10.1038/369330a0 |
| format | Article |
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1,2
. IL-2 can signal through high or intermediate affinity receptors which contain IL-2Rα (refs 3, 4) + β (refs5–8) + γ (ref. 9) or β + γ chains, respectively. IL-2Rγ is a common γ chain, γ
c
, also shared by the IL-7 (ref. 10) and IL-4 (refs 11,12) receptors, which when mutated results in X-linked severe combined immunodeficiency
13
. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the β- and γ
c
-chain cytoplasmic domains. Anti-I L-2Rα monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracel-lular domains of IL-2Rβ and γ
c
are replaced by that of IL-2Rα. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2Rα and that the β-transmembrane domain is not required for receptor chain inter-actions. Finally, we provide a method for mapping residues in the γ
c
cytoplasmic domain even in cells that constitutively express γ
c
.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/369330a0</identifier><identifier>PMID: 8183373</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Antibodies, Bispecific ; Antibodies, Monoclonal ; Biological and medical sciences ; Biopolymers ; Cell Division - immunology ; Cell Line ; Cell receptors ; Cell structures and functions ; Cellular biology ; Cytoplasm - immunology ; Fundamental and applied biological sciences. Psychology ; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors ; Humanities and Social Sciences ; Humans ; letter ; Medical research ; Mice ; Molecular and cellular biology ; multidisciplinary ; Mutation ; Receptors, Interleukin-2 - chemistry ; Receptors, Interleukin-2 - physiology ; Recombinant Fusion Proteins ; Science ; Science (multidisciplinary) ; Signal Transduction - immunology ; Structure-Activity Relationship</subject><ispartof>Nature (London), 1994-05, Vol.369 (6478), p.330-333</ispartof><rights>Springer Nature Limited 1994</rights><rights>1994 INIST-CNRS</rights><rights>Copyright Macmillan Journals Ltd. May 26, 1994</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3140-7dc3ea40cb428d767074fdbc254172c03ac85446ab21f79d850c823bc78be8e73</citedby><cites>FETCH-LOGICAL-c3140-7dc3ea40cb428d767074fdbc254172c03ac85446ab21f79d850c823bc78be8e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/369330a0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/369330a0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4063294$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8183373$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakamura, Yoshlaki</creatorcontrib><creatorcontrib>Russell, Sarah M.</creatorcontrib><creatorcontrib>Mess, Sarah A.</creatorcontrib><creatorcontrib>Friedmann, Michael</creatorcontrib><creatorcontrib>Erdos, Michael</creatorcontrib><creatorcontrib>Francois, Christine</creatorcontrib><creatorcontrib>Jacques, Yannick</creatorcontrib><creatorcontrib>Adelstein, Stephen</creatorcontrib><creatorcontrib>Leonard, Warren J.</creatorcontrib><title>Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>THE interaction of interleukin-2 (IL-2) and IL-2 receptors criti-cally regulates the T-cell immune response following antigen activation
1,2
. IL-2 can signal through high or intermediate affinity receptors which contain IL-2Rα (refs 3, 4) + β (refs5–8) + γ (ref. 9) or β + γ chains, respectively. IL-2Rγ is a common γ chain, γ
c
, also shared by the IL-7 (ref. 10) and IL-4 (refs 11,12) receptors, which when mutated results in X-linked severe combined immunodeficiency
13
. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the β- and γ
c
-chain cytoplasmic domains. Anti-I L-2Rα monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracel-lular domains of IL-2Rβ and γ
c
are replaced by that of IL-2Rα. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2Rα and that the β-transmembrane domain is not required for receptor chain inter-actions. Finally, we provide a method for mapping residues in the γ
c
cytoplasmic domain even in cells that constitutively express γ
c
.</description><subject>Animals</subject><subject>Antibodies, Bispecific</subject><subject>Antibodies, Monoclonal</subject><subject>Biological and medical sciences</subject><subject>Biopolymers</subject><subject>Cell Division - immunology</subject><subject>Cell Line</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Cellular biology</subject><subject>Cytoplasm - immunology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>letter</subject><subject>Medical research</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Receptors, Interleukin-2 - chemistry</subject><subject>Receptors, Interleukin-2 - physiology</subject><subject>Recombinant Fusion Proteins</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal Transduction - immunology</subject><subject>Structure-Activity Relationship</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkc9q3DAQxkVJSTdpoS9QEKGE9OB29MeSfCyhbQILvTRnI0vjjYJtbST7kD5W-x55pijsJoX20NPAfL_5ZoaPkLcMPjIQ5pNQjRBg4QVZMalVJZXRB2QFwE0FRqhX5CjnGwComZaH5NAwI4QWK7K5wBlT9GHEFH7aOcSJxp7O10gv1xWnCR1u55jo_a-K2snT-9-Vu7Zhou5ujtvB5jE46uNYWpmGXAZul5DQ074M5bCZ7DCEafOavOztkPHNvh6Tq69ffpxfVOvv3y7PP68rJ5iESnsn0EpwneTGa6VBy953jteSae5AWGdqKZXtOOt1400NznDROW06NKjFMTnd-W5TvF0wz-0YssNhsBPGJbdaSa3B1P8FmTKyMU1TwJO_wJu4pPJWbjmUU7QUj25nO8ilmHPCvt2mMNp01zJoHxNqnxIq6Lu939KN6J_BfSRFf7_XbXZ26JOdXMjPmAQleCML9mGH5aJMG0x_zvpn5QMjG6UL</recordid><startdate>19940526</startdate><enddate>19940526</enddate><creator>Nakamura, Yoshlaki</creator><creator>Russell, Sarah M.</creator><creator>Mess, Sarah A.</creator><creator>Friedmann, Michael</creator><creator>Erdos, Michael</creator><creator>Francois, Christine</creator><creator>Jacques, Yannick</creator><creator>Adelstein, Stephen</creator><creator>Leonard, Warren J.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7X8</scope></search><sort><creationdate>19940526</creationdate><title>Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling</title><author>Nakamura, Yoshlaki ; Russell, Sarah M. ; Mess, Sarah A. ; Friedmann, Michael ; Erdos, Michael ; Francois, Christine ; Jacques, Yannick ; Adelstein, Stephen ; Leonard, Warren J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3140-7dc3ea40cb428d767074fdbc254172c03ac85446ab21f79d850c823bc78be8e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Antibodies, Bispecific</topic><topic>Antibodies, Monoclonal</topic><topic>Biological and medical sciences</topic><topic>Biopolymers</topic><topic>Cell Division - immunology</topic><topic>Cell Line</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Cellular biology</topic><topic>Cytoplasm - immunology</topic><topic>Fundamental and applied biological sciences. 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Academic</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakamura, Yoshlaki</au><au>Russell, Sarah M.</au><au>Mess, Sarah A.</au><au>Friedmann, Michael</au><au>Erdos, Michael</au><au>Francois, Christine</au><au>Jacques, Yannick</au><au>Adelstein, Stephen</au><au>Leonard, Warren J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>1994-05-26</date><risdate>1994</risdate><volume>369</volume><issue>6478</issue><spage>330</spage><epage>333</epage><pages>330-333</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>THE interaction of interleukin-2 (IL-2) and IL-2 receptors criti-cally regulates the T-cell immune response following antigen activation
1,2
. IL-2 can signal through high or intermediate affinity receptors which contain IL-2Rα (refs 3, 4) + β (refs5–8) + γ (ref. 9) or β + γ chains, respectively. IL-2Rγ is a common γ chain, γ
c
, also shared by the IL-7 (ref. 10) and IL-4 (refs 11,12) receptors, which when mutated results in X-linked severe combined immunodeficiency
13
. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the β- and γ
c
-chain cytoplasmic domains. Anti-I L-2Rα monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracel-lular domains of IL-2Rβ and γ
c
are replaced by that of IL-2Rα. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2Rα and that the β-transmembrane domain is not required for receptor chain inter-actions. Finally, we provide a method for mapping residues in the γ
c
cytoplasmic domain even in cells that constitutively express γ
c
.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>8183373</pmid><doi>10.1038/369330a0</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 1994-05, Vol.369 (6478), p.330-333 |
| issn | 0028-0836 1476-4687 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals; Nature |
| subjects | Animals Antibodies, Bispecific Antibodies, Monoclonal Biological and medical sciences Biopolymers Cell Division - immunology Cell Line Cell receptors Cell structures and functions Cellular biology Cytoplasm - immunology Fundamental and applied biological sciences. Psychology Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors Humanities and Social Sciences Humans letter Medical research Mice Molecular and cellular biology multidisciplinary Mutation Receptors, Interleukin-2 - chemistry Receptors, Interleukin-2 - physiology Recombinant Fusion Proteins Science Science (multidisciplinary) Signal Transduction - immunology Structure-Activity Relationship |
| title | Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling |
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