Interferon alpha activates the tyrosine kinase Lyn in haemopoietic cells.
We investigated whether the src-family tyrosine kinase Lyn is involved in the generation of interferon alpha (IFN alpha) signals in haemopoietic cells. In vitro kinase assays using IFN alpha-sensitive cells of B-cell origin demonstrated the presence of IFN alpha-dependent kinase activity in anti-Lyn immunoprecipitates. Further studies demonstrated that Lyn associates via its src homology 2 (SH2) domain with the Janus family tyrosine kinase Tyk-2. This interaction was IFN alpha-dependent and involved direct binding of the SH2 domain of Lyn to the IFN alpha-activated form of Tyk-2. Thus, during binding of IFN alpha to its receptor in malignant haemopoietic cells, Lyn is engaged in an IFN alpha-signalling pathway, probably downstream of Tyk-2.
Uddin
S
S
Department of Medicine, University of Illinois at Chicago and West Side Veterans Affairs Hospital, 60607-7173, USA.
Grumbach
I M
IM
Yi
T
T
Colamonici
O R
OR
Platanias
L C
LC
D015153:Blotting, Western; D002450:Cell Communication; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
D016898:Interferon-alpha; D011505:Protein-Tyrosine Kinases