Phosphorylation of ATF2 and interaction with NFY induces c-Jun in the gonadotrope.

Induction of c-Jun and c-Fos, partners that comprise the AP1 transcription factor, is critical for GnRH regulation of FSHβ gene expression. The signaling pathways that are necessary for regulation of AP1 in the gonadotrope cell are not known. Here, we investigate the mechanism of c-Jun induction by GnRH, the sole regulator of c-Jun in the gonadotrope. We identify that GnRH phosphorylates ATF2 via p38 and JNK, the same pathways responsible for GnRH induction of c-Jun. Upon phosphorylation, ATF2 binds the CRE element within the c-Jun proximal promoter and interacts with NFY. Functional ATF2 is necessary for both GnRH induction of c-Jun and FSHβ. Taken together, these studies elucidate the specificity of c-Jun induction by GnRH in the gonadotrope by demonstrating GnRH activation of the p38 and JNK signaling pathways that lead to phosphorylation of ATF2, providing critical insight into GnRH regulation of its target gene, the gonadotropin subunit FSHβ.