Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function

Immunity. 2000 Oct;13(4):561-71. doi: 10.1016/s1074-7613(00)00055-8.


Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNalpha, although a high concentration of IFNalpha can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNalpha-dependent signaling while being required in mediating IL-12-dependent biological responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Mammalian
  • Gene Targeting
  • Interferon-alpha / physiology*
  • Interleukin-10 / physiology
  • Interleukin-12 / physiology*
  • Interleukin-6 / physiology
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mutagenesis, Insertional
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / physiology*
  • Proteins / genetics
  • Proteins / physiology*
  • Signal Transduction / immunology*
  • Stem Cells
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • TYK2 Kinase
  • Transfection


  • Interferon-alpha
  • Interleukin-6
  • Proteins
  • Interleukin-10
  • Interleukin-12
  • Protein-Tyrosine Kinases
  • TYK2 Kinase
  • Tyk2 protein, mouse