PHOSPHOLIPID REGULATION OF A CYCLIC AMP-SPECIFIC PHOSPHODIESTERASE (PDE4) FROM U937 CELLS

The regulation of phosphodiesterase-4 (PDE4) by various phospholipids was explored using PDE4s partially purified from U937 cells. Preincuba tion (5 min, 4 degrees C) of the large molecular weight PDE4 denoted ' 'Peak 2 PDE4'' with mixed phosphatidic acids (PAs) produced a 2-fold i ncrease in its V-max without changing its K-m (similar to 2 mu M) for cyclic AMP. This ''activation'' was not limited to PAs with specific f atty acid substituents: Synthetic PAs containing saturated and/or unsa turated fatty acids 16-20 carbons long produced similar effects. Lysop hosphatidic acids (LPAs) and phosphatidylserines (PSs) also induced PD E4 activation, whereas phosphatidylcholines (PCs), phosphatidylethanol amines (PEs) and diacylglycerol did not. Antibodies to a peptide regio n near the PDE4 catalytic site specifically inhibited PA-induced activ ation. The data demonstrate that anionic phospholipids can act as non- essential activators of a leukocyte PDE4, and suggest biochemical cros stalk between phospholipid-dependent and cyclic AMP-dependent signalli ng pathways in human leukocytes.