PMID- 10542297
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - Catalytically active TYK2 is essential for interferon-beta-mediated
      phosphorylation of STAT3 and interferon-alpha receptor-1 (IFNAR-1) but not for
      activation of phosphoinositol 3-kinase.
PG  - 32507-11
AB  - TYK2, a Janus kinase, plays both structural and catalytic roles in type I
      interferon (IFN) signaling. We recently reported (Rani, M. R. S., Gauzzi, C.,
      Pellegrini, S., Fish, E., Wei, T., and Ransohoff, R. M. (1999) J. Biol. Chem.
      274, 1891-1897) that catalytically active TYK2 was necessary for IFN-beta to
      induce the beta-R1 gene. We now report IFN-beta-mediated activation of STATs and 
      other components in U1 (TYK2-null) cell lines that were complemented with
      kinase-negative (U1.KR930) or wild-type TYK2 (U1.wt). We found that IFN-beta
      induced phosphorylation on tyrosine of STAT3 in U1.wt cells but not in U1.KR930
      cells, whereas STAT1 and STAT2 were activated in both cell lines. Additionally,
      IFN-beta-mediated phosphorylation of interferon-alpha receptor-1 (IFNAR-1) was
      defective in IFN-beta treated U1.KR930 cells, but evident in U1.wt cells. In
      U1A-derived cells, the p85/p110 phosphoinositol 3-kinase isoform was associated
      with IFNAR-1 but not STAT3, and the association was ligand-independent. Further, 
      IFN-beta treatment stimulated IFNAR-1-associated phosphoinositol kinase activity 
      equally in either U1.wt or U1.KR930 cells. Our results indicate that
      catalytically active TYK2 is required for IFN-beta-mediated tyrosine
      phosphorylation of STAT3 and IFNAR-1 in intact cells.
FAU - Rani, M R
AU  - Rani MR
AD  - Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic
      Foundation, Cleveland, Ohio 44195, USA.
FAU - Leaman, D W
AU  - Leaman DW
FAU - Han, Y
AU  - Han Y
FAU - Leung, S
AU  - Leung S
FAU - Croze, E
AU  - Croze E
FAU - Fish, E N
AU  - Fish EN
FAU - Wolfman, A
AU  - Wolfman A
FAU - Ransohoff, R M
AU  - Ransohoff RM
LA  - eng
GR  - 1PO1 CA62220/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IFNAR1 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Interferon)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 156986-95-7 (Receptor, Interferon alpha-beta)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (TYK2 Kinase)
RN  - EC 2.7.10.2 (TYK2 protein, human)
SB  - IM
MH  - Catalysis
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Interferon-beta/*metabolism
MH  - Membrane Proteins
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proteins/*metabolism
MH  - Receptor, Interferon alpha-beta
MH  - Receptors, Interferon/*metabolism
MH  - STAT3 Transcription Factor
MH  - Signal Transduction
MH  - TYK2 Kinase
MH  - Trans-Activators/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.32507 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):32507-11. doi: 10.1074/jbc.274.45.32507.