Prolactin activates the interferon-regulated p91 transcription factor and the Jak2 kinase by tyrosine phosphorylation.
The prolactin (PRL) receptor is a member of the family of cytokine receptors that lack intrinsic tyrosine kinase activity but contain two conserved cysteines in their N-terminal regions and a WSXWS motif adjacent to their transmembrane domains. In a manner similar to the interferons (IFNs), exposure of cells to PRL results in tyrosine phosphorylation of several cellular proteins and the rapid transcriptional induction of the IFN regulatory factor 1 gene. In this communication, we demonstrate that treatment of rat Nb2 lymphoma cells with PRL activates a latent protein factor so that it binds to an enhancer in the IFN regulatory factor 1 gene. This enhancer has been shown to be required for IFN-gamma-activated expression of this gene. PRL-induced assembly of the DNA binding complex, PRL-stimulated factor, required tyrosine phosphorylation. PRL-stimulated factor contained at least one protein that was antigenically similar to the p91 transcription factor, a component of several transcription complexes required for cytokine-activated gene expression. PRL not only induced the tyrosine phosphorylation of p91 but also induced tyrosine phosphorylation of Jak2, a tyrosine kinase required for IFN-gamma-activated gene expression. These results provide evidence for a signaling mechanism, some of whose components are shared by both PRL and IFN-gamma receptors, that results in the expression of early response genes.
David
M
M
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Bethesda, MD 20892.
Petricoin
E F
EF
Igarashi
K
K
Feldman
G M
GM
Finbloom
D S
DS
Larner
A C
AC
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D007372:Interferons / Q000502:physiology*; D053614:Janus Kinase 2; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011388:Prolactin / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C494081:Stat1 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D014443:Tyrosine; D011388:Prolactin; D004247:DNA; D007372:Interferons; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; C507927:Jak2 protein, rat; D053614:Janus Kinase 2