Spatiotemporal dynamics of lipid second messenger signaling

Protein kinases B (Akt), C, and D are regulated by lipid second messengers: 3’phosphoinositides for protein kinase B and diacylglycerol for protein kinases C and D. Using genetically‐encoded reporters for each of these kinases, we have determined the spatiotemporal dynamics of lipid second messenger signaling mediated by each of these kinases at defined intracellular locations. Although all three kinases are rapidly activated at the plasma membrane, we find that all three kinases have robust and much more sustained activity at the Golgi. In addition, tethering of the reporters to specific scaffolds for each of these kinases reveals highly localized activation within the microenvironment of the scaffold. These results underscore the importance of subcellular location and scaffolding in lipid second messenger signaling.