Disruption of the CD4-p56lck complex is required for rapid internalization of CD4
CD4 is a cell surface glycoprotein expressed by a subset of T lymphocytes and functions to enhance T-cell activation. CD4 is noncovalently associated via the cytoplasmic domain with the protein-tyrosine kinase p56lck, a member of the src protein-tyrosine kinase family. Upon activation of protein kin...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1992-08, Vol.89 (16), p.7566-7570 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | SLECKMAN, B. P SHIN, J IGRAS, V. E COLLINS, T. L STROMINGER, J. L BURAKOFF, S. J |
| description | CD4 is a cell surface glycoprotein expressed by a subset of T lymphocytes and functions to enhance T-cell activation. CD4 is noncovalently associated via the cytoplasmic domain with the protein-tyrosine kinase p56lck, a member of the src protein-tyrosine kinase family. Upon activation of protein kinase C by phorbol ester, CD4 is phosphorylated on cytoplasmic serine residues and internalized from the cell surface, and disruption of the CD4-p56lck complex occurs. The exact relationship between these events is likely to be functionally significant, as cytoplasmic-domain serine phosphorylation and internalization have been shown to regulate the function of receptors that possess intrinsic protein-tyrosine kinase activity. Here we demonstrate that p56lck slows the rate of phorbol 12-myristate 13-acetate-induced internalization of CD4 in a manner that depends on a physical association between p56lck and CD4. This decreased rate is due at least in part to a requirement for disruption of the CD4-p56lck complex prior to internalization of CD4. Furthermore, disruption of the CD4-p56lck complex appears to depend on the integrity of the cytoplasmic-domain serine at position 408, probably due to a requirement for phosphorylation. |
| doi_str_mv | 10.1073/pnas.89.16.7566 |
| format | Article |
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P ; SHIN, J ; IGRAS, V. E ; COLLINS, T. L ; STROMINGER, J. L ; BURAKOFF, S. J</creator><creatorcontrib>SLECKMAN, B. P ; SHIN, J ; IGRAS, V. E ; COLLINS, T. L ; STROMINGER, J. L ; BURAKOFF, S. J</creatorcontrib><description>CD4 is a cell surface glycoprotein expressed by a subset of T lymphocytes and functions to enhance T-cell activation. CD4 is noncovalently associated via the cytoplasmic domain with the protein-tyrosine kinase p56lck, a member of the src protein-tyrosine kinase family. Upon activation of protein kinase C by phorbol ester, CD4 is phosphorylated on cytoplasmic serine residues and internalized from the cell surface, and disruption of the CD4-p56lck complex occurs. The exact relationship between these events is likely to be functionally significant, as cytoplasmic-domain serine phosphorylation and internalization have been shown to regulate the function of receptors that possess intrinsic protein-tyrosine kinase activity. Here we demonstrate that p56lck slows the rate of phorbol 12-myristate 13-acetate-induced internalization of CD4 in a manner that depends on a physical association between p56lck and CD4. This decreased rate is due at least in part to a requirement for disruption of the CD4-p56lck complex prior to internalization of CD4. Furthermore, disruption of the CD4-p56lck complex appears to depend on the integrity of the cytoplasmic-domain serine at position 408, probably due to a requirement for phosphorylation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.89.16.7566</identifier><identifier>PMID: 1502168</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Acad Sciences</publisher><subject>Antigens, CD - genetics ; Antigens, CD - metabolism ; Biological and medical sciences ; CD4 Antigens - genetics ; CD4 Antigens - isolation & purification ; CD4 Antigens - metabolism ; CD8 Antigens - metabolism ; Cell Membrane - immunology ; Cloning, Molecular ; Fluorescent Antibody Technique ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; HeLa Cells ; Humans ; Immunobiology ; Kinetics ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Lymphocytes - enzymology ; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation ; Plasmids ; Protein-Tyrosine Kinases - isolation & purification ; Protein-Tyrosine Kinases - metabolism ; Tetradecanoylphorbol Acetate - pharmacology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1992-08, Vol.89 (16), p.7566-7570</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3836-198ec3840e9d105690c521c4c951018d6f1c31590033a47e4461573d133d61943</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/89/16.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC49751/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC49751/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5535175$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1502168$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SLECKMAN, B. P</creatorcontrib><creatorcontrib>SHIN, J</creatorcontrib><creatorcontrib>IGRAS, V. E</creatorcontrib><creatorcontrib>COLLINS, T. L</creatorcontrib><creatorcontrib>STROMINGER, J. L</creatorcontrib><creatorcontrib>BURAKOFF, S. J</creatorcontrib><title>Disruption of the CD4-p56lck complex is required for rapid internalization of CD4</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>CD4 is a cell surface glycoprotein expressed by a subset of T lymphocytes and functions to enhance T-cell activation. CD4 is noncovalently associated via the cytoplasmic domain with the protein-tyrosine kinase p56lck, a member of the src protein-tyrosine kinase family. Upon activation of protein kinase C by phorbol ester, CD4 is phosphorylated on cytoplasmic serine residues and internalized from the cell surface, and disruption of the CD4-p56lck complex occurs. The exact relationship between these events is likely to be functionally significant, as cytoplasmic-domain serine phosphorylation and internalization have been shown to regulate the function of receptors that possess intrinsic protein-tyrosine kinase activity. Here we demonstrate that p56lck slows the rate of phorbol 12-myristate 13-acetate-induced internalization of CD4 in a manner that depends on a physical association between p56lck and CD4. This decreased rate is due at least in part to a requirement for disruption of the CD4-p56lck complex prior to internalization of CD4. Furthermore, disruption of the CD4-p56lck complex appears to depend on the integrity of the cytoplasmic-domain serine at position 408, probably due to a requirement for phosphorylation.</description><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - metabolism</subject><subject>Biological and medical sciences</subject><subject>CD4 Antigens - genetics</subject><subject>CD4 Antigens - isolation & purification</subject><subject>CD4 Antigens - metabolism</subject><subject>CD8 Antigens - metabolism</subject><subject>Cell Membrane - immunology</subject><subject>Cloning, Molecular</subject><subject>Fluorescent Antibody Technique</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>Kinetics</subject><subject>Lymphocyte Specific Protein Tyrosine Kinase p56(lck)</subject><subject>Lymphocytes - enzymology</subject><subject>Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation</subject><subject>Plasmids</subject><subject>Protein-Tyrosine Kinases - isolation & purification</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Tetradecanoylphorbol Acetate - pharmacology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1Lw0AQhhdRav04e1L2IHhKnel-JAtepH6CIIKel3WzsatpEndTqf56U1pbvXiagfd5ZuAl5ABhgJCy06YycZCpAcpBKqTcIH0EhYnkCjZJH2CYJhkf8m2yE-MrACiRQY_0UMAQZdYnDxc-hmnT-rqidUHbsaOjC540Qpb2jdp60pRuRn2kwb1PfXA5LepAg2l8Tn3VulCZ0n-ZH79z98hWYcro9pdzlzxdXT6ObpK7--vb0fldYlnGZIIqc93GwakcQUgFVgzRcqsEAma5LNAyFAqAMcNTx7lEkbIcGcslKs52ydnibjN9nrjcuqoNptRN8BMTPnVtvP6bVH6sX-oPzVUqsNNPF7oNdYzBFSsTQc-r1fNqdaY0Sj2vtjMOfz9c84suu_x4mZtoTVkEU1kfV5gQTGAqOuxkic3v_6TrP7qYlmXrZm1HHv1Lsm_5VZiZ</recordid><startdate>19920815</startdate><enddate>19920815</enddate><creator>SLECKMAN, B. P</creator><creator>SHIN, J</creator><creator>IGRAS, V. E</creator><creator>COLLINS, T. L</creator><creator>STROMINGER, J. L</creator><creator>BURAKOFF, S. J</creator><general>National Acad Sciences</general><general>National Academy of Sciences of the United States of America</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>5PM</scope></search><sort><creationdate>19920815</creationdate><title>Disruption of the CD4-p56lck complex is required for rapid internalization of CD4</title><author>SLECKMAN, B. P ; SHIN, J ; IGRAS, V. E ; COLLINS, T. L ; STROMINGER, J. L ; BURAKOFF, S. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3836-198ec3840e9d105690c521c4c951018d6f1c31590033a47e4461573d133d61943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - metabolism</topic><topic>Biological and medical sciences</topic><topic>CD4 Antigens - genetics</topic><topic>CD4 Antigens - isolation & purification</topic><topic>CD4 Antigens - metabolism</topic><topic>CD8 Antigens - metabolism</topic><topic>Cell Membrane - immunology</topic><topic>Cloning, Molecular</topic><topic>Fluorescent Antibody Technique</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>Kinetics</topic><topic>Lymphocyte Specific Protein Tyrosine Kinase p56(lck)</topic><topic>Lymphocytes - enzymology</topic><topic>Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation</topic><topic>Plasmids</topic><topic>Protein-Tyrosine Kinases - isolation & purification</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Tetradecanoylphorbol Acetate - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SLECKMAN, B. P</creatorcontrib><creatorcontrib>SHIN, J</creatorcontrib><creatorcontrib>IGRAS, V. E</creatorcontrib><creatorcontrib>COLLINS, T. L</creatorcontrib><creatorcontrib>STROMINGER, J. L</creatorcontrib><creatorcontrib>BURAKOFF, S. J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SLECKMAN, B. P</au><au>SHIN, J</au><au>IGRAS, V. E</au><au>COLLINS, T. L</au><au>STROMINGER, J. L</au><au>BURAKOFF, S. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disruption of the CD4-p56lck complex is required for rapid internalization of CD4</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1992-08-15</date><risdate>1992</risdate><volume>89</volume><issue>16</issue><spage>7566</spage><epage>7570</epage><pages>7566-7570</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>CD4 is a cell surface glycoprotein expressed by a subset of T lymphocytes and functions to enhance T-cell activation. CD4 is noncovalently associated via the cytoplasmic domain with the protein-tyrosine kinase p56lck, a member of the src protein-tyrosine kinase family. Upon activation of protein kinase C by phorbol ester, CD4 is phosphorylated on cytoplasmic serine residues and internalized from the cell surface, and disruption of the CD4-p56lck complex occurs. The exact relationship between these events is likely to be functionally significant, as cytoplasmic-domain serine phosphorylation and internalization have been shown to regulate the function of receptors that possess intrinsic protein-tyrosine kinase activity. Here we demonstrate that p56lck slows the rate of phorbol 12-myristate 13-acetate-induced internalization of CD4 in a manner that depends on a physical association between p56lck and CD4. This decreased rate is due at least in part to a requirement for disruption of the CD4-p56lck complex prior to internalization of CD4. Furthermore, disruption of the CD4-p56lck complex appears to depend on the integrity of the cytoplasmic-domain serine at position 408, probably due to a requirement for phosphorylation.</abstract><cop>Washington, DC</cop><pub>National Acad Sciences</pub><pmid>1502168</pmid><doi>10.1073/pnas.89.16.7566</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1992-08, Vol.89 (16), p.7566-7570 |
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| language | eng |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Antigens, CD - genetics Antigens, CD - metabolism Biological and medical sciences CD4 Antigens - genetics CD4 Antigens - isolation & purification CD4 Antigens - metabolism CD8 Antigens - metabolism Cell Membrane - immunology Cloning, Molecular Fluorescent Antibody Technique Fundamental and applied biological sciences. Psychology Fundamental immunology HeLa Cells Humans Immunobiology Kinetics Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Lymphocytes - enzymology Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation Plasmids Protein-Tyrosine Kinases - isolation & purification Protein-Tyrosine Kinases - metabolism Tetradecanoylphorbol Acetate - pharmacology |
| title | Disruption of the CD4-p56lck complex is required for rapid internalization of CD4 |
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