Association of the interferon-dependent tyrosine kinase Tyk-2 with the hematopoietic cell phosphatase

J Biol Chem. 1995 Aug 4;270(31):18179-82. doi: 10.1074/jbc.270.31.18179.


The tyrosine kinase Tyk-2 is physically associated with the Type I interferon (IFN) receptor complex and is rapidly activated during IFN alpha stimulation. We report that Tyk-2 forms stable complexes with the SH2-containing hematopoietic cell phosphatase (HCP) in several hematopoietic cell lines in vivo, and that the IFN alpha-induced tyrosine-phosphorylated form of Tyk-2 is a substrate for the phosphatase activity of HCP in in vitro assays. Furthermore, treatment of cells with the phosphatase inhibitor sodium orthovanadate induces tyrosine phosphorylation of Tyk-2 and an associated 115-kDa protein. Altogether, these data suggest that HCP regulates tyrosine phosphorylation of the Tyk-2 kinase, and thus its function may be important in the transmission of signals generated at the Type I IFN receptor level.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Hematopoietic Stem Cells / enzymology
  • Hematopoietic Stem Cells / metabolism*
  • Interferon-alpha / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Janus Kinase 1
  • Phosphorylation / drug effects
  • Precipitin Tests
  • Protein Binding
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • Tumor Cells, Cultured
  • Vanadates / pharmacology


  • Interferon-alpha
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Receptors, Interferon
  • Recombinant Fusion Proteins
  • Receptor, Interferon alpha-beta
  • Vanadates
  • Protein-Tyrosine Kinases
  • Janus Kinase 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases