Gene/Protein
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Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:3.6.3.1 (
Mg2+-ATPase
)
1,484
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cardiac sarcoplasmic reticulum plays a critical role in the excitation-contraction cycle and hormonal regulation of heart cells. Catecholamines exert their ionotropic action through the regulation of calcium transport into the sarcoplasmic reticulum. Cyclic 3'-5'-adenosine monophosphate (cAMP) causes the cAMP-dependent protein kinase to phosphorylate the regulatory protein
phospholamban
, which results in the stimulation of calcium transport. Calmodulin also phosphorylates
phospholamban
by a calcium-dependent mechanism. We have reported the isolation and purification of
phospholamban
with low deoxycholate (DOC) concentrations (5 X 10(-6) M). We have also reported the isolation and purification of Ca2+ +
Mg2+-ATPase
with a similar procedure. Both
phospholamban
and Ca2+ +
Mg2+-ATPase
retained their native properties associated with sarcoplasmic reticulum vesicles. Further, we have shown that the removal of
phospholamban
from membranes of sarcoplasmic reticulum vesicles uncouples Ca2+-uptake from ATPase without any effect on Ca2+ +
Mg2+-ATPase
activity or Ca2+ efflux. Phospholamban appears to be the substrate for both the Ca2+-calmodulin system and the cAMP-dependent protein kinase system. It is found that the phosphorylation of
phospholamban
by the Ca2+-calmodulin system is required for the normal basal level of Ca2+ transport, and that the phosphorylation of
phospholamban
at another site by the cAMP-dependent protein kinase system causes the stimulation of Ca2+-transport above the basal level. The functional effects of the phosphorylation of
phospholamban
by cAMP-dependent protein kinase system are expressed only after the phosphorylation of
phospholamban
with Ca2+-calmodulin system. We propose a model for the cardiac Ca2+ +
Mg2+-ATPase
, whereby the enzyme is normally uncoupled from Ca2+ uptake. The enzyme becomes coupled to Ca2+ transport after the first site of
phospholamban
is phosphorylated with the Ca2+-calmodulin system. When the second site of
phospholamban
is phosphorylated with cAMP-dependent protein kinase both Ca2+ transport and ATPase are stimulated and
phospholamban
becomes inaccessible to DOC solubilization and trypsin.
...
PMID:Role of phospholamban in regulating cardiac sarcoplasmic reticulum calcium pump. 614 39
