Diacylglycerol Kinase ϵ Is Selective for Both Acyl Chains of Phosphatidic Acid or Diacylglycerol

摘要: The phosphatidylinositol (PI) cycle mediates many cellular events by controlling the metabolism of lipid second messengers. Diacylglycerol kinase ϵ (DGKϵ) has an important role in this cycle. DGKϵ is only DGK isoform to show inhibition its product phosphatidic acid (PA) as well substrate specificity for sn-2 arachidonoyl-diacylglycerol (DAG). Here, we that and are both determined selectivity a combination sn-1 acyl chains PA or DAG, respectively, preferring most prevalent chain composition lipids involved specifically PI cycle, 1-stearoyl-2-arachidonoyl. Although difference rate closely related species small, there significant enrichment 1-stearoyl-2-arachidonoyl because cyclical nature turnover. We also competitive deletion hydrophobic segment cationic cluster does not affect DAG. Thus, active site recognizes headgroup but two propose mechanism regulation where dual used negatively regulate enzymatic activity manner ensures remains committed turnover This novel enzyme within signaling pathway could serve template enzymes other pathways cell.