Phospholipid regulation of a cyclic AMP-specific phosphodiesterase (PDE4) from U937 cells

Cell Signal. 1995 Nov;7(8):827-35. doi: 10.1016/0898-6568(95)02010-1.

Abstract

The regulation of phosphodiesterase-4 (PDE4) by various phospholipids was explored using PDE4s partially purified from U937 cells. Preincubation (5 min, 4 degrees 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 (approximately 2 microM) 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.

Publication types

  • Comparative Study

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases*
  • Amino Acid Sequence
  • Animals
  • Antibody Formation
  • Cyclic AMP / metabolism*
  • Cyclic GMP / pharmacology
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Enzyme Activation / drug effects
  • Fatty Acids / analysis
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lysophospholipids / pharmacology
  • Molecular Sequence Data
  • Monocytes / drug effects*
  • Monocytes / enzymology
  • Neoplasm Proteins / metabolism
  • Peptide Fragments / immunology
  • Phosphatidic Acids / pharmacology
  • Phosphatidylcholines / pharmacology
  • Phospholipids / chemistry
  • Phospholipids / pharmacology*
  • Phosphoric Diester Hydrolases / chemistry
  • Phosphoric Diester Hydrolases / immunology
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyrrolidinones / pharmacology
  • Rabbits
  • Rolipram
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects

Substances

  • Fatty Acids
  • Lysophospholipids
  • Neoplasm Proteins
  • Peptide Fragments
  • Phosphatidic Acids
  • Phosphatidylcholines
  • Phospholipids
  • Pyrrolidinones
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclic GMP
  • Rolipram