M. David et al., PROLACTIN ACTIVATES THE INTERFERON-REGULATED P91 TRANSCRIPTION FACTORAND THE JAK2 KINASE BY TYROSINE PHOSPHORYLATION, Proceedings of the National Academy of Sciences of the United Statesof America, 91(15), 1994, pp. 7174-7178
The prolactin (PRL) receptor is a member of the family of cytokine rec
eptors that lack intrinsic tyrosine kinase activity but contain two co
nserved cysteines in their N-terminal regions and a WSXWS moth adjacen
t to their transmembrane domains. In a manner similar to the interfero
ns (IFNs), exposure of cells to PRL results in tyrosine phosphorylatio
n of several cellular proteins and the rapid transcriptional induction
of the IFN regulatory factor 1 gene. In this communication, we demons
trate that treatment of rat Nb2 lymphoma cells with PRL activates a la
tent protein factor so that it binds to an enhancer in the IFN regulat
ory 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 phosphor
ylation. 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 b
ut also induced tyrosine phosphorylation of Jak2, a tyrosine kinase re
quired for IFN-gamma-activated gene expression. These results provide
evidence for a signaling mechanism, some of whose components are share
d by both PRL and IFN-gamma receptors, that results in the expression
of early response genes.