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
Hauptverfasser: COLAMONICI, O. R, UYTTENDAELE, H, DOMANSKI, P, HAI YAN, KROLEWSKI, J. J
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container_end_page 3522
container_issue 5
container_start_page 3518
container_title The Journal of biological chemistry
container_volume 269
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
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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 &amp; 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. 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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. 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ispartof The Journal of biological chemistry, 1994-02, Vol.269 (5), p.3518-3522
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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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