Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-9-13
pubmed:abstractText
We previously demonstrated that the gene tyk2 rescues the phenotype of a human mutant cell line unresponsive to alpha (IFN) and partially responsive to IFN-beta. Here, we describe functional complementation of the mutant cells with the corresponding cDNA. To characterize the putative non-receptor protein tyrosine kinase encoded by the gene tyk2 and begin to understand its functioning, we have raised polyclonal antibodies against a segment of the protein. Using these, we have identified tyk2 as a 134-kDa protein which is rapidly and transiently phosphorylated on tyrosine in response to IFN-alpha/beta and possesses an inducible kinase activity when tested in vitro. IFN-gamma has no effect on the phosphorylation state of the protein. In agreement with previous genetic evidence, these results assign a role to tyk2 in the IFN-alpha/beta signalling pathway and not in the IFN-gamma pathway. Fractionation of cell lysates have helped to localize the bulk of the protein in the cytoplasm, with a minor fraction associated with the cell membrane. Both protein pools undergo activation upon short-term IFN treatment of intact cells. Through the study of the effect of pervanadate on the phosphorylation level and the activity of tyk2, we conclude that activation of tyk2 by IFN-alpha does not require an intermediate regulatory tyrosine phosphatase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
223
pubmed:geneSymbol
tyk2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
427-35
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:8055912-Cell Membrane, pubmed-meshheading:8055912-Cells, Cultured, pubmed-meshheading:8055912-Cytosol, pubmed-meshheading:8055912-DNA, Complementary, pubmed-meshheading:8055912-Enzyme Activation, pubmed-meshheading:8055912-Gene Expression Regulation, Enzymologic, pubmed-meshheading:8055912-HeLa Cells, pubmed-meshheading:8055912-Humans, pubmed-meshheading:8055912-Immunoblotting, pubmed-meshheading:8055912-Interferon Type I, pubmed-meshheading:8055912-Interferon-beta, pubmed-meshheading:8055912-Interferon-gamma, pubmed-meshheading:8055912-Molecular Weight, pubmed-meshheading:8055912-Mutation, pubmed-meshheading:8055912-Phenotype, pubmed-meshheading:8055912-Phosphorylation, pubmed-meshheading:8055912-Protein-Tyrosine Kinases, pubmed-meshheading:8055912-Proteins, pubmed-meshheading:8055912-Recombinant Proteins, pubmed-meshheading:8055912-TYK2 Kinase
pubmed:year
1994
pubmed:articleTitle
Activation of the protein tyrosine kinase tyk2 by interferon alpha/beta.
pubmed:affiliation
Unité INSERM 276, Institut Pasteur, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't