Protein kinase A (PKA) interferes with the processing and activity of sterol regulatory element binding proteins (SREBPs)

• DOI: 10.1096/fasebj.27.1_supplement.585.4
• Publication Date: 2021-06-16T10:30:06Z
• Authors: Ryan Magadan Esquejo; Peter E. Phelan; Manuel Roqueta‐Ri...; Timothy F. Osborne
• Keywords: Brefeldin A

Several kinases are known to modulate the activity of sterol regulatory element binding proteins (SREBPs), which transcription factors that activate lipid biosynthesis. The inactive SREBP precursor forms bound endoplasmic reticulum (ER) and require cleavage activating protein (SCAP) shuttle SREBPs Golgi, where proteases cleave release active SREBPs, can then enter nucleus transcription. be down‐regulated by conditions PKA is higher such as glucagon action in liver; however, a mechanism explain this effect lacking. Here, we show block processing various cells types. We used forskolin induce found lower levels mature SREBP‐1 BCR‐ABL transformed bone marrow. also H‐89, inhibitor, marrow, HeLa cells, mouse primary hepatocytes. Preliminary results showed H‐89 injection into mice blunt negative on accumulation liver. In preliminary studies, amounts SCAP Golgi when added Chinese hamster ovary (CHO) stably express GFP‐SCAP. There conserved putative phosphorylation motif many phosphoproteomic studies site phosphorylated different settings. Thus, our recent discovery points novel role for trafficking activation, possibly via direct SCAP.