Evidence for the participation of a Ca2+-dependent protein kinase and a protein phosphatase in the regulation of the Ca2+ transport ATPase of the sarcoplasmic reticulum. 1. Effect of inhibitors of the Ca2+-dependent protein kinase and protein phosphatase

Biochemistry ◽  
1978 ◽  
Vol 17 (5) ◽  
pp. 759-766 ◽  
Author(s):  
Walter H. Hoerl ◽  
Herbert P. Jennissen ◽  
Ludwig M. G. Heilmeyer
Keyword(s):  
Protein Kinase ◽  
Sarcoplasmic Reticulum ◽  
Protein Phosphatase ◽  
Dependent Protein Kinase ◽  
Transport Atpase ◽  
Dependent Protein ◽  
Effect Of Inhibitors

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.

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