PDE4D antibody

Background of PDE4D antibody

Enzymes of the cAMP-dependent phosphodiesterase type 4 (PDE4) family are important in hydrolyzing cAMP produced by G-protein coupled receptor (GPCR) stimulated adenylyl cyclases. In brain more than 90% of cAMP formed by the stimulation of GPCRs is hydrolyzed by PDE4 enzymes (1). Members of the PDE4A, B and D family are associated with GPCRs (adrenergic and dopaminergic) signaling (6, 7).
ERK mitogen activated protein kinase and cAMP pathways are important regulators for cross talk between protein kinases and cAMP at distinct points in the cell (2). The phosphodiesterase type 4b, C and D sbtypes, but not the PDE4A subtype, have a consensus ERK site phosphorylation site. This site in PDE4D3 lies at serine at position 579 (3-5). The ERK kinase phosphorylation site lies in the consensus motif Pro-Xaa-Ser-Pro. In vivo, a KIM motif (Val-Xaa-Xaa-Lys-Lys-Xaa6-Leu-Leu-Leu-Xaa12-Phospho-serine) serves as a docking site for ERK/JNK and is located upstream to the target phosphorylation site. The specificty for ERK is confered over JNK by the presence of FQF motif down stream from the phosphorylation site (6). PDE4B, C and D all have conserved KIM and FQF sites that provide serine as substrate for ERK phosphorylation. The crystal structure and the three dimentional modeling of the PDE4 D/B suggest that both KIM and FQF domain are located on a single microdoamin, the KIM being located on exposed hair pin loop and the FQF on an exposed a helix (6). The location of these doamins excelently displaced for ERK internations.
The phosphorylation of PDE4B, C, D long-form variants by ERK kinases led to a significant inhibition (approximately 80%) in PDEase activity (3-5). ERK phosphorylation of PDE4 long-forms cause an increse in cAMP as a resultof inhibition in PDEase activity. The rise in cAMP levels consequentially activated the cAMP-dependent PKA that phosphorylates the same protiens at PKA site (serine 53 in PDE4D3) that led to a significant increase in PDEase activity (7). Taken together these effects will generate a traanssient increase in cAMP lervels in a cytosolic sub-compartment.