Abstract
The regulation of phosphodiesterase-4 (PDE4) by various phospholipids was explored using PDE4 partially purified from U937 cells. Preincubation (5 min, 4°C) of the large molecular weight PDE4 denoted "Peak 2 PDE4" with mixed phosphatidic acids (PAs) produced a 2-fold increase in its Vmax without changing its Km (∼2 μM) for cyclic AMP. This "activation" was not limited to PAs with specific fatty acid substituents: Synthetic PAs containing saturated and/or unsaturated fatty acids 16-20 carbons long produced similar effects. Lysophosphatidic acids (LPAs) and phosphatidylserines (PSs) also induced PDE4 activation, whereas phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and diacylglycerol did not. Antibodies to a peptide region near the PDE4 catalytic site specifically inhibited PA-induced activation. The data demonstrate that anionic phospholipids can act as non-essential activators of a leukocyte PDE4, and suggest biochemical crosstalk between phospholipid-dependent and cyclic AMP-dependent signalling pathways in human leukocytes.
Original language | English (US) |
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Pages (from-to) | 827-835 |
Number of pages | 9 |
Journal | Cellular Signalling |
Volume | 7 |
Issue number | 8 |
DOIs | |
State | Published - Nov 1995 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Cell Biology