Growth Hormone Regulates Phosphorylation and Function of CCAAT/Enhancer-binding Protein b by Modulating Akt and

Growth hormone (GH) regulates transcription factors associated with c-fos, including C/EBPb. Two forms of C/EBPb, liver-activating protein (LAP) and liver inhibi-tory protein (LIP), are dephosphorylated in GH-treated 3T3-F442A fibroblasts. GH-induced dephosphorylation of LAP and LIP is reduced when cells are preincubated with phosphatidylinositol 3*-kinase (PI3K) inhibitors. GH activates Akt and inhibits glycogen synthase ki-nase-3 (GSK-3). Lithium, a GSK-3 inhibitor, increases GH-dependent dephosphorylation of LAP and LIP. Both are in vitro substrates of GSK-3, suggesting that GSK-3 inactivation contributes to GH-promoted dephosphoryl-ation of C/EBPb. Alkaline phosphatase increases bind-ing of LAP homodimers and decreases binding of LIP homodimers to c-fos, suggesting that dephosphorylatio