Activation of a cyclic nucleotide phosphodiesterase 4 (PDE4) from rat thymocytes by phosphatidic acid.
The cytosolic cyclic nucleotide phosphodiesterase (PDE) activity from rat thymocytes was resolved into five peaks by HPLC. Only two forms of the cAMP-specific PDE4 were found to be sensitive to physiologically relevant phosphatidic acid (PA) concentrations. PA activated the PDE4-peak 3 form, the fatty acid composition and unsaturation degree determining the efficiency of PA. The PDE4-peak 2 form was inhibited only by PA with saturated fatty acyl groups. PDE4 activation was specific of anionic phospholipids, a free phosphate group in the phospholipid molecule being required for maximum activation. These results suggest that PA may contribute to the lowering of cAMP level required in the early steps of a lympho-proliferative response, thus regulating immune functions through PDE4 activation.
Savany
A
A
INSERM U.352, Laboratoire de Biochimie et Pharmacologie, INSA-Lyon, Villeurbanne, France.
Abriat
C
C
Némoz
G
G
Lagarde
M
M
Prigent
A F
AF
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000818:Animals; D002478:Cells, Cultured; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D008055:Lipids / Q000494:pharmacology; D008297:Male; D010712:Phosphatidic Acids / Q000737:chemistry / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology*
D008055:Lipids; D010712:Phosphatidic Acids; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4