Phospholamban

Phospholamban, also known as PLN or PLB, is a is_associated_with::protein that in humans is encoded by the PLN is_associated_with::gene. Phospholamban is a 52-is_associated_with::amino acid is_associated_with::integral membrane protein that regulates the Ca2+ pump in is_associated_with::cardiac muscle and is_associated_with::skeletal muscle cells.

Function
This protein is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase (PKA) in cardiac muscle. The protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca++-ATPase (is_associated_with::SERCA) in the unphosphorylated state, but inhibition is relieved upon is_associated_with::phosphorylation of the protein. The subsequent activation of the Ca++ pump leads to shorter intervals between contractions, thereby contributing to the is_associated_with::lusitropic response elicited in heart by beta-agonists. The protein is a key regulator of  cardiac diastolic function. Mutations in this gene are a cause of inherited human is_associated_with::dilated cardiomyopathy with refractory is_associated_with::congestive heart failure.

When phospholamban is is_associated_with::phosphorylated by PKA its ability to inhibit the sarcoplasmic reticulum calcium pump (SERCA) is lost. Thus, activators of PKA, such as the beta-adrenergic agonist is_associated_with::epinephrine (released by sympathetic stimulation), may enhance the rate of cardiac myocyte relaxation. In addition, since SERCA is more active, the next is_associated_with::action potential will cause an increased release of calcium, resulting in increased contraction (positive is_associated_with::inotropic effect). When phospholamban is not phosphorylated, such as when PKA is inactive, it can interact with and inhibit SERCA. The overall effect of phospholamban is to decrease negatively_regulates_biological_process::contractility and the rate of negatively_regulates_biological_process::muscle relaxation, thereby decreasing stroke volume and heart rate, respectively.

Clinical significance
Gene knockout of phospholamban results in animals with hyperdynamic hearts, with little apparent negative consequence.

Mutations in this gene are a cause of inherited human dilated associated_with_disease::cardiomyopathy with refractory associated_with_disease::congestive heart failure.

Discovery
Phospholamban was discovered by is_associated_with::Arnold Martin Katz and coworkers in 1974.

Interactions
PLN has been shown to interact with SLN and is_associated_with::ATP2A1.