PMID: 20484118

 

    Legend: Gene, Sites

Title : Inhibition of phospholamban phosphorylation by O-GlcNAcylation: implications for diabetic cardiomyopathy

Abstract :
  1. Cardiac-type sarco(endo)plasmic reticulum Ca(2 )- ATPase ( SERCA2a ) plays a major role in cardiac muscle contractility
  2. Phospholamban ( PLN ) regulates the function of SERCA2a via its Ser(16)-phosphorylation
  3. Since it has been proposed that the Ser/Thr residues on cytoplasmic and nuclear proteins are modified by O-linked N-acetylglucosamine (O-GlcNAc), we examined the effect of O-GlcNAcylation on PLN function in rat adult cardiomyocytes
  4. Studies using enzymatic labeling and co-immunoprecipitation of wild type and a series of mutants of PLN showed that PLN was O-GlcNAcylated and Ser(16) of PLN might be the site for O-GlcNAcylation
  5. In cardiomyocytes treated with O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), the O-GlcNAcylation was significantly increased compared to non-treated cells
  6. Simultaneously, Ser(16)-phosphorylation of PLN was reduced
  7. In Chinese hamster ovary cells where PLN cDNA and O-GlcNAc transferase siRNA were co-transfected, the Ser(16)-phosphorylation of PLN was significantly increased compared to controls
  8. The same results were observed in heart homogenates from diabetic rats
  9. In a co-immunoprecipitation of PLN with SERCA2a , the physical interaction between the two proteins was increased in PUGNAc-treated cardiomyocytes
  10. Unlike non-treated cells, the activity of SERCA2a and the profiles of calcium transients in PUGNAc-treated cardiomyocytes were not significantly changed even after treatment with catecholamine
  11. These data suggest that PLN is O-GlcNAcylated to induce the inhibition of its phosphorylation, which correlates to the deterioration of cardiac function
  12. This might define a novel mechanism by which PLN regulation of SERCA2a is altered under conditions where O-GlcNAcylation is increased, such as those occurring in diabetes
Output (sent_index, trigger, protein, sugar, site):
  • 3. modified, , -, O-GlcNAc, residues
  • 3. modified, , -, O-linked N-acetylglucosamine, residues
Output(Part-Of) (sent_index, protein, site):
  • 3. proteins, residues
  • 4. PLN, Ser(16)
  • 4. PLN, site
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

Protein NCBI ID SENTENCE INDEX
PLN 64672 2,3,4,6,7,9,11,12
Phospholamban 64672 2
phospholamban 64672 0