RECEPTOR TO NUCLEUS SIGNALING BY PROLACTIN AND INTERLEUKIN-2 VIA ACTIVATION OF LATENT DNA-BINDING FACTORS

The mechanism of action of prolactin (PRL), a lactogenic and immunoreg ulatory hormone, has remained undetermined despite its critical role i n development. This study identifies a DNA-binding factor induced by P RL that appears to mediate a signal from the cell surface receptor to specific gene expression in the nucleus. PRL stimulates the proliferat ion of Nb2 T-lymphoma cells and activates transcription of the interfe ron-regulatory factor 1 (IRF-1) gene. Within minutes of PRL stimulatio n, a PRL-induced factor (PRLIF) is activated and binds to a target sit e in the promoter of the IRF-1 gene. The PRLIF-binding site contains a n inverted GAAA repeat that is also functional in the hormone-responsi ve beta-casein gem. The PRL-receptor complex signals tyrosine phosphor ylation of JAK2, a nonreceptor tyrosine kinase, which may lead to acti vation of PRLIF. T-cell proliferation and transcriptional activation o f the IRF-1 gene is also induced by the cytokine interleukin 2 (IL-2). This report demonstrates the rapid activation of an IL-2 nuclear-acti vated factor that recognizes the same GAAA inverted repeat in the IRF- 1 promoter. PRLIF and IL-2 nuclear-activated factor are newly identifi ed factors that appear to serve fundamental roles in the signal transd uction pathways of PRL and IL-2, respectively, leading to the transcri ptional regulation of responsive genes.