RGD Reference Report - Post-translational modification regulates prostaglandin D2 synthase apoptotic activity: characterization by site-directed mutagenesis. - Rat Genome Database

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Post-translational modification regulates prostaglandin D2 synthase apoptotic activity: characterization by site-directed mutagenesis.

Authors: Ragolia, L  Hall, CE  Palaia, T 
Citation: Ragolia L, etal., Prostaglandins Other Lipid Mediat. 2007 Feb;83(1-2):25-32. Epub 2006 Nov 7.
RGD ID: 1642585
Pubmed: PMID:17259069   (View Abstract at PubMed)
PMCID: PMC1805777   (View Article at PubMed Central)
DOI: DOI:10.1016/j.prostaglandins.2006.09.006   (Journal Full-text)

Lipocalin-type prostaglandin D(2) synthase (L-PGDS) is a highly glycosylated protein found in several body fluids. Elevated L-PGDS levels have been observed in the serum of patients with renal impairment, diabetes mellitus, and hypertension. Recently, we demonstrated the ability of L-PGDS to induce apoptosis in a variety of cell types including epithelial cells, neuronal cells, and vascular smooth muscle cells (VSMCs). The aim of this study was to investigate the effect several site-directed mutations had on L-PGDS-induced apoptosis in order to identify potential sites of regulation. Point mutations created in a glycosylation site (Asn51), a protein kinase C phosphorylation site (Ser106), and the enzymatic active site (Cys65) all inhibited L-PGDS-induced apoptosis as determined by both terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) and caspase3 activity. We also compared the L-PGDS isoforms present in GK rat serum to WKY control serum using two-dimensional gel electrophoresis and observed distinct differences which vanished after PNGase F glycolytic digestion. We conclude that post-translational modification of L-PGDS, by either glycosylation or phosphorylation, enhances its apoptotic activity and inhibits VSMC hyperproliferation and postulate that this process is altered in type 2 diabetes.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PtgdsRatextracellular space  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgds  (prostaglandin D2 synthase)


Additional Information