Prolactin activates the interferon-regulated p91 transcription factor and the Jak2 kinase by tyrosine phosphorylation

Michael David*, Emanuel F. Petricoin, Ken Ichi Igarashi, Gerald M. Feldman, David S. Finbloom, Andrew C. Larner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


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-γ-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-γ-activated gene expression. These results provide evidence for a signaling mechanism, some of whose components are shared by both PRL and IFN-γ receptors, that results in the expression of early response genes.

Original languageEnglish
Pages (from-to)7174-7178
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - 19 Jul 1994
Externally publishedYes


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