p135tyk2, an interferon-alpha-activated tyrosine kinase, is physically associated with an interferon-alpha receptor
Recent genetic studies have linked the tyk2 gene, which encodes a novel type of non-receptor tyrosine kinase, to the interferon-alpha intracellular signaling pathway. In this report, biochemical evidence is presented which supports this proposed function for the tyk2 tyrosine kinase and further defi...
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Veröffentlicht in: | The Journal of biological chemistry 1994-02, Vol.269 (5), p.3518-3522 |
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creator | COLAMONICI, O. R UYTTENDAELE, H DOMANSKI, P HAI YAN KROLEWSKI, J. J |
description | Recent genetic studies have linked the tyk2 gene, which encodes a novel type of non-receptor tyrosine kinase, to the interferon-alpha
intracellular signaling pathway. In this report, biochemical evidence is presented which supports this proposed function for
the tyk2 tyrosine kinase and further defines its role in the interferon-alpha signaling cascade. Specifically, the tyk2 gene
is shown to encode a 135-kDa protein which is rapidly phosphorylated on tyrosine in response to interferon-alpha treatment.
Indirect evidence suggests that the tyrosine phosphorylation of p135tyk2 is the result of autokinase activity, implying that
the Tyk2 tyrosine kinase is activated by interferon-alpha treatment. Two complementary methods demonstrate a physical association
between p135tyk2 and the alpha-subunit of the interferon-alpha receptor. First, immunoblots show that monoclonal antibodies
against the alpha-subunit of the interferon-alpha receptor can co-immunoprecipitate p135tyk2. Second, interferon-alpha receptor
proteins which have been labeled by affinity cross-linking with 125I-interferon-alpha 2 can be co-immunoprecipitated using
anti-tyk2 antisera. Taken together, these data suggest that an interferon-alpha receptor-p135tyk2 complex functions, in a
manner analogous to the CD4-lck tyrosine kinase complex, to initiate the interferon-alpha signaling cascade. |
doi_str_mv | 10.1016/S0021-9258(17)41893-X |
format | Article |
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intracellular signaling pathway. In this report, biochemical evidence is presented which supports this proposed function for
the tyk2 tyrosine kinase and further defines its role in the interferon-alpha signaling cascade. Specifically, the tyk2 gene
is shown to encode a 135-kDa protein which is rapidly phosphorylated on tyrosine in response to interferon-alpha treatment.
Indirect evidence suggests that the tyrosine phosphorylation of p135tyk2 is the result of autokinase activity, implying that
the Tyk2 tyrosine kinase is activated by interferon-alpha treatment. Two complementary methods demonstrate a physical association
between p135tyk2 and the alpha-subunit of the interferon-alpha receptor. First, immunoblots show that monoclonal antibodies
against the alpha-subunit of the interferon-alpha receptor can co-immunoprecipitate p135tyk2. Second, interferon-alpha receptor
proteins which have been labeled by affinity cross-linking with 125I-interferon-alpha 2 can be co-immunoprecipitated using
anti-tyk2 antisera. Taken together, these data suggest that an interferon-alpha receptor-p135tyk2 complex functions, in a
manner analogous to the CD4-lck tyrosine kinase complex, to initiate the interferon-alpha signaling cascade.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(17)41893-X</identifier><identifier>PMID: 8106393</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>Animals ; Antibodies, Monoclonal ; Base Sequence ; Biological and medical sciences ; Cell Line ; Cell receptors ; Cell structures and functions ; Cloning, Molecular ; DNA Primers ; DNA, Complementary - metabolism ; Enzyme Activation ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; HeLa Cells ; Humans ; Immunoblotting ; Interferon-alpha - metabolism ; Interferon-alpha - pharmacology ; Miscellaneous ; Molecular and cellular biology ; Molecular Sequence Data ; Moths ; Protein Biosynthesis ; Protein-Tyrosine Kinases - metabolism ; Proteins - isolation & purification ; Proteins - metabolism ; Receptor, Interferon alpha-beta ; Receptors, Interferon - metabolism ; Recombinant Fusion Proteins - biosynthesis ; Recombinant Fusion Proteins - metabolism ; Signal Transduction ; Transfection ; TYK2 Kinase</subject><ispartof>The Journal of biological chemistry, 1994-02, Vol.269 (5), p.3518-3522</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c254x-5af0b8998ca5785d5e11266c8b2e301451ce1f54cb54aa9d0379d111a016a3513</citedby><cites>FETCH-LOGICAL-c254x-5af0b8998ca5785d5e11266c8b2e301451ce1f54cb54aa9d0379d111a016a3513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4001361$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8106393$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>COLAMONICI, O. R</creatorcontrib><creatorcontrib>UYTTENDAELE, H</creatorcontrib><creatorcontrib>DOMANSKI, P</creatorcontrib><creatorcontrib>HAI YAN</creatorcontrib><creatorcontrib>KROLEWSKI, J. J</creatorcontrib><title>p135tyk2, an interferon-alpha-activated tyrosine kinase, is physically associated with an interferon-alpha receptor</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Recent genetic studies have linked the tyk2 gene, which encodes a novel type of non-receptor tyrosine kinase, to the interferon-alpha
intracellular signaling pathway. In this report, biochemical evidence is presented which supports this proposed function for
the tyk2 tyrosine kinase and further defines its role in the interferon-alpha signaling cascade. Specifically, the tyk2 gene
is shown to encode a 135-kDa protein which is rapidly phosphorylated on tyrosine in response to interferon-alpha treatment.
Indirect evidence suggests that the tyrosine phosphorylation of p135tyk2 is the result of autokinase activity, implying that
the Tyk2 tyrosine kinase is activated by interferon-alpha treatment. Two complementary methods demonstrate a physical association
between p135tyk2 and the alpha-subunit of the interferon-alpha receptor. First, immunoblots show that monoclonal antibodies
against the alpha-subunit of the interferon-alpha receptor can co-immunoprecipitate p135tyk2. Second, interferon-alpha receptor
proteins which have been labeled by affinity cross-linking with 125I-interferon-alpha 2 can be co-immunoprecipitated using
anti-tyk2 antisera. Taken together, these data suggest that an interferon-alpha receptor-p135tyk2 complex functions, in a
manner analogous to the CD4-lck tyrosine kinase complex, to initiate the interferon-alpha signaling cascade.</description><subject>Animals</subject><subject>Antibodies, Monoclonal</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Cloning, Molecular</subject><subject>DNA Primers</subject><subject>DNA, Complementary - metabolism</subject><subject>Enzyme Activation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Interferon-alpha - metabolism</subject><subject>Interferon-alpha - pharmacology</subject><subject>Miscellaneous</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Moths</subject><subject>Protein Biosynthesis</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proteins - isolation & purification</subject><subject>Proteins - metabolism</subject><subject>Receptor, Interferon alpha-beta</subject><subject>Receptors, Interferon - metabolism</subject><subject>Recombinant Fusion Proteins - biosynthesis</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Signal Transduction</subject><subject>Transfection</subject><subject>TYK2 Kinase</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEtP3DAQgC1URLfQn4AUVVXVSoR64jixjwi1pRISB0DamzVxJsQlm6R2tjT_Hu9De2Iuc5hvXh9j58AvgUPx_Z7zDFKdSfUVym85KC3S5RFbAFciFRKW79jigLxnH0L4w2PkGk7YiQJeCC0WLIwg5DQ_ZxcJ9onrJ_IN-aFPsRtbTNFO7h9OVCfT7IfgekqeXY-BLhIXkrGdg7PYdXOCIQzWbckXN7VvDUs8WRqnwZ-x4wa7QB_3-ZQ9_vzxcH2T3t79-n19dZvaTOb_U4kNr5TWyqIslawlAWRFYVWVkeCQS7AEjcxtJXNEXXNR6hoAMNrBKECcsi-7uaMf_q4pTGblgqWuw56GdTBlIaTQmYig3IE2_hg8NWb0boV-NsDNRrbZyjYbkwZKs5VtlrHvfL9gXa2oPnTt7cb6530dQ9TUeOytCwcs5xxEsbnz0w5r3VP74jyZyg22pZXJCm2kib8o8Qp_epOR</recordid><startdate>19940204</startdate><enddate>19940204</enddate><creator>COLAMONICI, O. R</creator><creator>UYTTENDAELE, H</creator><creator>DOMANSKI, P</creator><creator>HAI YAN</creator><creator>KROLEWSKI, J. J</creator><general>American Society for Biochemistry and Molecular Biology</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>7X8</scope></search><sort><creationdate>19940204</creationdate><title>p135tyk2, an interferon-alpha-activated tyrosine kinase, is physically associated with an interferon-alpha receptor</title><author>COLAMONICI, O. R ; UYTTENDAELE, H ; DOMANSKI, P ; HAI YAN ; KROLEWSKI, J. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c254x-5af0b8998ca5785d5e11266c8b2e301451ce1f54cb54aa9d0379d111a016a3513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Cloning, Molecular</topic><topic>DNA Primers</topic><topic>DNA, Complementary - metabolism</topic><topic>Enzyme Activation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Interferon-alpha - metabolism</topic><topic>Interferon-alpha - pharmacology</topic><topic>Miscellaneous</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Moths</topic><topic>Protein Biosynthesis</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proteins - isolation & purification</topic><topic>Proteins - metabolism</topic><topic>Receptor, Interferon alpha-beta</topic><topic>Receptors, Interferon - metabolism</topic><topic>Recombinant Fusion Proteins - biosynthesis</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Signal Transduction</topic><topic>Transfection</topic><topic>TYK2 Kinase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>COLAMONICI, O. R</creatorcontrib><creatorcontrib>UYTTENDAELE, H</creatorcontrib><creatorcontrib>DOMANSKI, P</creatorcontrib><creatorcontrib>HAI YAN</creatorcontrib><creatorcontrib>KROLEWSKI, J. 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>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>COLAMONICI, O. R</au><au>UYTTENDAELE, H</au><au>DOMANSKI, P</au><au>HAI YAN</au><au>KROLEWSKI, J. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p135tyk2, an interferon-alpha-activated tyrosine kinase, is physically associated with an interferon-alpha receptor</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1994-02-04</date><risdate>1994</risdate><volume>269</volume><issue>5</issue><spage>3518</spage><epage>3522</epage><pages>3518-3522</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>Recent genetic studies have linked the tyk2 gene, which encodes a novel type of non-receptor tyrosine kinase, to the interferon-alpha
intracellular signaling pathway. In this report, biochemical evidence is presented which supports this proposed function for
the tyk2 tyrosine kinase and further defines its role in the interferon-alpha signaling cascade. Specifically, the tyk2 gene
is shown to encode a 135-kDa protein which is rapidly phosphorylated on tyrosine in response to interferon-alpha treatment.
Indirect evidence suggests that the tyrosine phosphorylation of p135tyk2 is the result of autokinase activity, implying that
the Tyk2 tyrosine kinase is activated by interferon-alpha treatment. Two complementary methods demonstrate a physical association
between p135tyk2 and the alpha-subunit of the interferon-alpha receptor. First, immunoblots show that monoclonal antibodies
against the alpha-subunit of the interferon-alpha receptor can co-immunoprecipitate p135tyk2. Second, interferon-alpha receptor
proteins which have been labeled by affinity cross-linking with 125I-interferon-alpha 2 can be co-immunoprecipitated using
anti-tyk2 antisera. Taken together, these data suggest that an interferon-alpha receptor-p135tyk2 complex functions, in a
manner analogous to the CD4-lck tyrosine kinase complex, to initiate the interferon-alpha signaling cascade.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>8106393</pmid><doi>10.1016/S0021-9258(17)41893-X</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
subjects | Animals Antibodies, Monoclonal Base Sequence Biological and medical sciences Cell Line Cell receptors Cell structures and functions Cloning, Molecular DNA Primers DNA, Complementary - metabolism Enzyme Activation Fundamental and applied biological sciences. Psychology Gene Expression HeLa Cells Humans Immunoblotting Interferon-alpha - metabolism Interferon-alpha - pharmacology Miscellaneous Molecular and cellular biology Molecular Sequence Data Moths Protein Biosynthesis Protein-Tyrosine Kinases - metabolism Proteins - isolation & purification Proteins - metabolism Receptor, Interferon alpha-beta Receptors, Interferon - metabolism Recombinant Fusion Proteins - biosynthesis Recombinant Fusion Proteins - metabolism Signal Transduction Transfection TYK2 Kinase |
title | p135tyk2, an interferon-alpha-activated tyrosine kinase, is physically associated with an interferon-alpha receptor |
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