Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation.

• DOI: 10.1128/mcb.13.5.2822
• Publication Date: 2015-10-06T00:34:27Z
• Authors: B E Wadzinski; W H Wheat; S Jaspers; L F Peruski; R L Lickteig; G L Johnson; D J Klemm
• Keywords: Dephosphorylation; Protein phosphatase 1; CREB1

Cyclic AMP (cAMP)-dependent protein kinase A (PKA) stimulates the transcription of many eucaryotic genes by catalyzing phosphorylation cAMP-regulatory element binding (CREB). Conversely, attenuation or inhibition cAMP-stimulated gene would require dephosphorylation CREB a nuclear phosphatase. In HepG2 cells treated with serine/threonine (Ser/Thr) phosphatase inhibitor okadaic acid, dibutyryl-cAMP-stimulated from phosphoenolpyruvate carboxykinase (PEPCK) promoter was enhanced over level PEPCK observed in dibutyryl-cAMP alone. This process mediated, at least part, region that binds CREB. Likewise, acid prevents PKA-phosphorylated rat liver extracts and enhances ability PKA to stimulate cell-free reactions. The enhance PKA-stimulated vitro entirely dependent on presence phospho-CREB (P-CREB) activity present coelutes Ser/Thr type 2A (PP2A) Mono Q, amino-hexyl Sepharose, heparin agarose columns chromatographically resolved Ser/Thr-phosphatase 1 (PP1). Furthermore, P-CREB unaffected heat-stable inhibitor-2, which is potent selective PP1. Nuclear PP2A dephosphorylated 30-fold more efficiently than did Finally, when immunopurified PP1, PP2A-treated not vitro, whereas PP1-treated retained transcription. appears be primary dephosphorylates