Fig. 4.

Downstream effectors of phospholipase D-generated lipid second messengers. Phospholipase D (PLD) hydrolyzes phosphatidylcholine to produce choline and phosphatidic acid (PA). PA can interact and modulate the activity of various downstream effectors such as the kinase suppressor of Ras (KSR), mammalian target of rapamycin (mTOR), phosphatidylinositol 4-phosphate 5-kinase (PI4P5K), phosphodiesterase 4D3 (PDE4D3), protein serine/threonine phosphatase 1 (PP1), the small GTP-binding proteins Rac and c-Raf, ribosomal S6 kinase (RSK), son of sevenless (SOS), Src homology region 2 domain-containing phosphatase-1 (SHP1), and nuclear hormone receptor steroidogenic factor-1 (SF-1). PA can be dephosphorylated by lipid phosphate phosphatases (LPPs) to yield diacylglycerol (DAG). DAG effectors include the classical and novel protein kinase C (PKC) isoenzymes, protein kinase D (PKD) family of protein kinases, the Ras guanine nucleotide release proteins (RasGRP), the Rac GTPase-activating proteins chimaerins, and UNC13 proteins.