PMID: 8593251Nov 1, 1995Paper

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

Cellular Signalling
M E DiSantoR J Heaslip

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.

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Citations

Sep 12, 1998·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·N T Ktistakis
Jun 12, 2003·Experimental Cell Research·Giovanna TabelliniAlberto M Martelli
Jun 1, 2001·Advances in Enzyme Regulation·L CoccoF A Manzoli
Jul 19, 2002·Advances in Enzyme Regulation·Gursant S KularShamshad Cockcroft
Nov 20, 1997·Comparative Biochemistry and Physiology. Part A, Physiology·M RöpkeO Frederiksen
May 24, 2000·The Journal of Steroid Biochemistry and Molecular Biology·L MrnkaJ Pácha
Oct 23, 1997·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·C D TomaL C Gerstenfeld
Jun 21, 2005·Il Farmaco·Annalisa TaitMario Baraldi

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