scholarly journals Stimulation of bovine cardiac sarcoplasmic reticulum Ca2+ pump and blocking of phospholamban phosphorylation and dephosphorylation by a phospholamban monoclonal antibody.

1986 ◽  
Vol 261 (15) ◽  
pp. 7018-7023
Author(s):  
T Suzuki ◽  
J H Wang
Keyword(s):  
Monoclonal Antibody ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Phospholamban Phosphorylation ◽  
Stimulation Of

scholarly journals Translation of Ser16 and Thr17 phosphorylation of phospholamban into Ca2+-pump stimulation

1996 ◽  
Vol 316 (1) ◽  
pp. 201-207 ◽  
Author(s):  
Wayne A. JACKSON ◽  
John COLYER
Keyword(s):  
Protein Kinase ◽  
Sarcoplasmic Reticulum ◽  
Dependent Protein Kinase ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Oligomeric Protein ◽  
Pump Activity ◽  
Dependent Protein ◽  
Indicator Dye ◽  
Phospholamban Phosphorylation ◽  
Stimulation Of

Stimulation of cardiac sarcoplasmic reticulum Ca2+-pump activity is achieved by phosphorylation of the oligomeric protein phospholamban at either Ser16 or Thr17. The altered mobility of phosphorylated forms of pentameric phospholamban has been utilized to demonstrate that the mechanisms of phosphorylation of the two sites differ. Phosphorylation of Ser16 by the AMP-dependent protein kinase proceeds via a random mechanism [Li, Wang and Colyer (1990) Biochemistry 29, 4535–4540], whereas phosphorylation of Thr17 by calmodulin-dependent protein kinase is shown here to proceed via a co-operative mechanism. This co-operative reaction mechanism was unaffected by the phosphorylation status of Ser16. These two mechanisms of phosphorylation generate very different phosphoprotein profiles depending on whether the Ser16 or Thr17 residue is phosphorylated. The translation of these patterns of phosphorylation into Ca2+-pump function was reviewed using a fluorimetric Ca2+-indicator dye, fluo-3, to measure Ca2+ uptake by cardiac sarcoplasmic reticulum vesicles. The rate of Ca2+ accumulation, which parallels Ca2+-pump activity, was stimulated in proportion with the stoichiometry of phospholamban phosphorylation, irrespective of whether phosphorylation was on Ser16 or Thr17.

scholarly journals Anti-phospholamban and protein kinase A alter the Ca2+ sensitivity and maximum velocity of Ca2+ uptake by the cardiac sarcoplasmic reticulum

1998 ◽  
Vol 331 (1) ◽  
pp. 245-249 ◽  
Author(s):  
Margaret E. KARGACIN ◽  
Zenobia ALI ◽  
Gary J. KARGACIN
Keyword(s):  
Protein Kinase ◽  
Sarcoplasmic Reticulum ◽  
Maximum Velocity ◽  
Functional Effect ◽  
Dependent Protein Kinase ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Dependent Protein ◽  
Uptake Velocity ◽  
Phospholamban Phosphorylation ◽  
Kinase A

The activity of the SERCA2a Ca2+ pump in the sarcoplasmic reticulum (SR) of cardiac muscle is inhibited by phospholamban. When phospholamban is phosphorylated by cyclic-AMP-dependent protein kinase (PKA) this inhibition is relieved. It is generally agreed that this results in an increase in the Ca2+ sensitivity of the SR Ca2+ pump; however, some investigators have also reported an increase in the maximum velocity of the pump. We have used a sensitive fluorescence method to measure net Ca2+ uptake by native cardiac SR vesicles and compared the effects of a constitutively active subunit of PKA (cPKA) with those of a monoclonal antibody (A1) that binds to phospholamban and is thought to mimic the effect of phosphorylation. Both the Ca2+ sensitivity and the maximum velocity of uptake were increased by cPKA and by A1. The effects of cPKA and A1 on uptake velocity were only slightly additive. No changes in uptake were detected with denatured cPKA or denatured A1. These results indicate that the functional effect of phospholamban phosphorylation is to increase both the Ca2+ sensitivity and the maximum velocity of net Ca2+ uptake into the SR.

Adenylyl cyclase type VI corrects cardiac sarcoplasmic reticulum calcium uptake defects in cardiomyopathy

2004 ◽  
Vol 287 (5) ◽  
pp. H1906-H1912 ◽  
Author(s):  
Tong Tang ◽  
Mei Hua Gao ◽  
David M. Roth ◽  
Tracy Guo ◽  
H. Kirk Hammond
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Adenylyl Cyclase ◽  
Calcium Uptake ◽  
Maximum Velocity ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Camp Generation ◽  
Plasmic Reticulum ◽  
Salutary Effect ◽  
Sarcoplasmic Reticulum Calcium ◽  
Phospholamban Phosphorylation

Calcium malfunction plays a central role in heart failure. Here, we provide evidence that adenylyl cyclase type VI restores sarco(endo)plasmic reticulum 2a (SERCA2a) affinity for calcium and maximum velocity of cardiac calcium uptake by sarcoplasmic reticulum in murine dilated cardiomyopathy. Restoration of normal SERCA2a affinity for calcium is associated not only with decreased phospholamban protein expression but also with increased phospholamban phosphorylation by PKA activation. The ratio of phosphorylated ryanodine receptor 2 (RyR2) to RyR2 protein was increased, but the amount of phosphorylated RyR2 was unaffected. These data provide a possible mechanism by which adenylyl cyclase type VI (in contrast to other signaling elements associated with increased cAMP generation) has a salutary effect in the failing heart.

Phospholamban phosphorylation increases the passive calcium leak from cardiac sarcoplasmic reticulum

2012 ◽  
Vol 464 (3) ◽  
pp. 295-305 ◽  
Author(s):  
Roozbeh Aschar-Sobbi ◽  
Teresa L. Emmett ◽  
Gary J. Kargacin ◽  
Margaret E. Kargacin
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Phospholamban Phosphorylation
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