Stat1 serine phosphorylation occurs independently of tyrosine phosphorylation and requires an activated Jak2 kinase.
Gamma interferon (IFN-gamma) induces both tyrosine and serine phosphorylation of Stat1. Stat1 serine phosphorylation is required for maximal transcriptional activity of Stat1. In this report, we present evidence that Stat1 tyrosine phosphorylation is not a prerequisite for Stat1 serine phosphorylation, although an active Jak2 kinase is required for both phosphorylation events. Stat1 serine phosphorylation occurs with a more delayed time course than tyrosine phosphorylation. The occurrence of serine phosphorylation without tyrosine phosphorylation suggests that serine phosphorylation takes place in the cytoplasm. Experiments performed with cells expressing either dominant-negative or constitutively active Ras protein indicated that the Ras-mitogen-activated protein kinase pathway is probably not involved in IFN-gamma-induced Stat1 serine phosphorylation. Finally, a kinase capable of correct Stat1 serine phosphorylation was detected in partially purified cytoplasmic extracts from both IFN-gamma-treated and untreated cells.
Zhu
X
X
Laboratory of Molecular Cell Biology, The Rockefeller University, New York, New York 10021, USA.
Wen
Z
Z
Xu
L Z
LZ
Darnell
J E
JE
D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D007371:Interferon-gamma / Q000494:pharmacology*; D053614:Janus Kinase 2; D051379:Mice; D010449:Peptide Mapping; D019606:Phosphoamino Acids / Q000032:analysis; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D004268:DNA-Binding Proteins; D019606:Phosphoamino Acids; D010748:Phosphopeptides; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014443:Tyrosine; D012694:Serine; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2