PROLACTIN ACTIVATES THE INTERFERON-REGULATED P91 TRANSCRIPTION FACTORAND THE JAK2 KINASE BY TYROSINE PHOSPHORYLATION

Citation
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
Citations number
45
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
00278424
Volume
91
Issue
15
Year of publication
1994
Pages
7174 - 7178
Database
ISI
SICI code
0027-8424(1994)91:15<7174:PATIPT>2.0.ZU;2-J
Abstract
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.