Figure 10. STAT-3 activity regulating the signaling network induced by BK or EGF in hypothalamic cells.

EGF-induced EGFR activation enhances ERK-1/2 activity, which leads to Ser-727 phosphorylation of STAT-3 and c-fos induction. Ser-727 phosphorylated STAT-3 together with AP-1 orchestrates transient SOCS-3 and putatively TRH expression via coactivation of SP-1, as indicated by the dashed arrow and previously proposed by others (69) TRH expression. BK-induced EGFR transactivation via src kinase and metalloproteases (MP) mimics the effects of EGF on ERK-1/2 and STAT-3. HB-EGF, heparin-binding EGF; PLC, phospholipase B.