Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Hematopoietic Stem Cells / enzymology
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Hematopoietic Stem Cells / metabolism*
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Interferon-alpha / pharmacology
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Intracellular Signaling Peptides and Proteins
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Janus Kinase 1
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Phosphorylation / drug effects
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Precipitin Tests
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Protein Binding
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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Proteins / genetics
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Proteins / metabolism*
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Receptor, Interferon alpha-beta
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Receptors, Interferon / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction*
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Tumor Cells, Cultured
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Vanadates / pharmacology
Substances
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Interferon-alpha
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Intracellular Signaling Peptides and Proteins
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Proteins
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Receptors, Interferon
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Recombinant Fusion Proteins
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Receptor, Interferon alpha-beta
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Vanadates
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Protein-Tyrosine Kinases
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Janus Kinase 1
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases