p135tyk2, an interferon-alpha-activated tyrosine kinase, is physically associated with an interferon-alpha receptor.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Colamonici, OR; Uyttendaele, H; Domanski, P; Yan, H; Krolewski, JJ

Published Date

  • February 4, 1994

Published In

Volume / Issue

  • 269 / 5

Start / End Page

  • 3518 - 3522

PubMed ID

  • 8106393

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng

Conference Location

  • United States