Regulation of Stat3 transcriptional activity by the conserved LPMSP motif for OSM and IL‐6 signaling

Abstract

To achieve maximal transcriptional activity in response to gp130 cytokines, Serine‐727 (Ser‐727) of Stat3 is phosphorylated. Ser‐727 resides in the LPMSP motif, the only conserved sequence among the transcription activation domains of several STATs. We show here that in addition to Ser‐727, other residues in this LPMSP motif are also required for Stat3 activity in response to cytokine signaling through regulation of Ser‐727 phosphorylation and recruitment of the transcription co‐activator CBP/p300 to the promoters of Stat3‐target genes for transcription activation. Hence, we have demonstrated a critical role for the whole conserved LPMSP motif in JAK‐STAT signaling.