Association of the interferon-dependent tyrosine kinase Tyk-2 with the hematopoietic cell phosphatase.
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.
Yetter
A
A
Division of Hematology-Oncology, Loyola University of Chicago, Maywood, Illinois 60153, USA.
Uddin
S
S
Krolewski
J J
JJ
Jiao
H
H
Yi
T
T
Platanias
L C
LC
D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000378:metabolism*; D016898:Interferon-alpha / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011485:Protein Binding; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology
D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D053633:Receptor, Interferon alpha-beta; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D053613:Janus Kinase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases