Modulation of mouse estrogen receptor transcription activity by protein kinase C δ

Abstract

The effect of protein kinase C (PKC) δ on the transcriptional activity of the mouse estrogen receptor was investigated. The receptor was expressed transiently in Cos-1 and NIH3T3 cells in the presence of wild-type, dominant negative or constitutively active forms of PKC δ. Transfection experiments demonstrated that PKC δ stimulated both unliganded and liganded estrogen receptor transcriptional activity. This stimulatory effect was not observed using PKC α or PKC ε. 4-Hydroxytamoxifen and the pure anti-estrogen ICI 164,384 reduced receptor transcriptional activity in the presence of PKC δ. The stimulatory effect of PKC δ on estrogen receptor transcriptional activity was mediated by the N-terminal activation function 1 (AF-1) domain. The reduced stimulatory effect of PKC δ on transcriptional activity of the phosphorylation defective mutant of estrogen receptor suggests that phosphorylation of serine 122 in the AF-1 region may mediate the modulatory effect of PKC δ. Wild-type PKC δ caused a twofold increase in estrogen receptor phosphorylation, while a dominant negative mutant of PKC δ reduced the receptor phosphorylation to five percent of that caused by wild-type PKC δ. Our results suggest that PKC δ participates in the signaling pathways that lead to estrogen receptor phosphorylation and its effect on estrogen receptor transcriptional activation is both cell type and promoter specific.