Ischemia‐induced phosphorylation of phospholemman directly activates rat cardiac Na/K ATPase

@article{Fuller2004IschemiainducedPO,
  title={Ischemia‐induced phosphorylation of phospholemman directly activates rat cardiac Na/K ATPase},
  author={William Fuller and Philip Eaton and James R Bell and Michael J. Shattock},
  journal={The FASEB Journal},
  year={2004},
  volume={18}
}
Regulation of the Na/K ATPase by protein kinases is model‐specific. We have observed a profound activation of the sarcolemmal Na/K ATPase during cardiac ischemia, which is masked by an inhibitor of the enzyme in the cytosol. The aim of these studies was to characterize the pathways involved in this activation in the Langendorff‐perfused rat heart. Na/K ATPase activity was determined by measuring ouabain‐sensitive phosphate generation by cardiac homogenates at 37°C. In isolated sarcolemma… 

Serine 68 phosphorylation of phospholemman: acute isoform-specific activation of cardiac Na/K ATPase.

Induced overexpression of phospholemman S68E mutant improves cardiac contractility and mortality after ischemia-reperfusion.

It is proposed that phosphorylated PLM may be a novel therapeutic target in ischemic heart disease and induced mice had similar survival as wild-type and noninduced mice.

Phospholemman-Phosphorylation Mediates the β-Adrenergic Effects on Na/K Pump Function in Cardiac Myocytes

It is concluded that PLM modulates the NKA function in a manner similar to the way phospholamban affects the related SR Ca-ATPase (inhibition of transport substrate affinity, that is relieved by phosphorylation).

Phosphorylation of Phospholemman (FXYD1) by Protein Kinases A and C Modulates Distinct Na,K-ATPase Isozymes*

Results indicate thatprotein kinase A phosphorylation of phospholemman has similar functional effects on Na,K-ATPase α1/β and α2/β isozymes and increases their apparent Na+ affinity, whereas protein kinase C modulates the transport activity of Na, K-ATpase α 2/β but not of α1/.

Expression and Phosphorylation of the Na-Pump Regulatory Subunit Phospholemman in Heart Failure

Reduced Na/K-ATPase expression in HF may be functionally offset by lower inhibition by PLM (because of reduced PLM expression and higher PLM phosphorylation), which is consistent with a role for PLM analogous to that of phospholamban for SR Ca-atPase (SERCA).

The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K ATPase

  • D. PavlovicW. FullerM. Shattock
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2007
It is concluded that unphosphorylated FXYD1 inhibits Na/K ATPase, whereas S68 phosphorylatedFXYD1 stimulates Na/k ATPase to a level above that seen in the absence of FXYD 1.

Phospholemman Inhibition of the Cardiac Na+/Ca2+ Exchanger

PLM, when phosphorylated at serine 68, inhibits Na+/Ca2+ exchange in the heart when co-expressed with NCX1, and mutating serine68 to glutamic acid resulted in additional suppression of INaCa as compared with wild-type PLM.

Phospholemman‐dependent regulation of the cardiac Na/K‐ATPase activity is modulated by inhibitor‐1 sensitive type‐1 phosphatase

This work provides the first physiological and biochemical evidence that PLM phosphorylation and cardiac Na/K‐ATPase activity are negatively regulated by PP‐1 and that this regulatory mechanism could be counteracted by I‐1.

Review Article: Phospholemman: A Novel Cardiac Stress Protein

The unique role of PLM in regulation of Na+‐K+‐ATPase, Na+/Ca2+ exchanger, and potentially L‐type Ca2+ channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in the armamentarium against heart failure.

Regulation of Cardiac Na+/Ca2+ Exchanger by Phospholemman

It is concluded that PLM regulates cardiac contractility by modulating the activities of NCX and Na+‐K+‐ATPase.
...

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