Synergistic Signaling in Fetal Brain by STAT3-Smad1 Complex Bridged by p300

Abstract

The cytokines LIF (leukemia inhibitory factor) and BMP2 (bone morphogenetic protein–2) signal through different receptors and transcription factors, namely STATs (signal transducers and activators of transcription) and Smads. LIF and BMP2 were found to act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacts physically with STAT3 at its amino terminus in a cytokine stimulation–independent manner, and with Smad1 at its carboxyl terminus in a cytokine stimulation–dependent manner. The formation of a complex between STAT3 and Smad1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neural progenitors.