Evidence for protein phosphatase inhibitor‐1 playing an amplifier role in β‐adrenergic signaling in cardiac myocytes

@article{ElArmouche2003EvidenceFP,
  title={Evidence for protein phosphatase inhibitor‐1 playing an amplifier role in $\beta$‐adrenergic signaling in cardiac myocytes},
  author={Ali El-Armouche and Thomas Rau and Oliver Zolk and Diana Ditz and Torsten Pamminger and Wolfram-Hubertus Zimmermann and Elmar J{\"a}ckel and Sian E. Harding and Peter Bokník and Joachim Neumann and Thomas Eschenhagen},
  journal={The FASEB Journal},
  year={2003},
  volume={17}
}
The protein phosphatase inhibitor‐1 (PPI‐1) inhibits phosphatase type‐1 (PP1) only when phosphorylated by protein kinase A and could play a pivotal role in the phosphorylation/dephosphorylation balance. Rat cardiac PPI‐1 was cloned by reverse transcriptase‐polymerase chain reaction, expressed in Eschericia coli, evaluated in phosphatase assays, and used to generate an antiserum. An adenovirus was constructed encoding PPI‐1 and green fluorescent protein (GFP) under separate cytomegalovirus… 
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Phospholemman‐dependent regulation of the cardiac Na/K‐ATPase activity is modulated by inhibitor‐1 sensitive type‐1 phosphatase
TLDR
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.
Inhibition of protein phosphatase 1 by inhibitor‐2 gene delivery ameliorates heart failure progression in genetic cardiomyopathy
  • M. Yamada, Y. Ikeda, M. Matsuzaki
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2006
TLDR
Results indicate that increased PP1 activity is an exacerbating factor during progression of genetic cardiomyopathy and modulation ofPP1 activity by INH‐2 provides a potential new treatment for HF without activating protein kinase A signaling in cardiomeocytes.
AAV-9 mediated phosphatase-1 inhibitor-1 overexpression improves cardiac contractility in unchallenged mice but is deleterious in pressure-overload
TLDR
The data suggest that AAV9-mediated cardiac-specific overexpression of I-1c, previously associated with enhanced calcium cycling, improves cardiac contractile function in unchallenged animals but failed to protect against cardiac remodeling induced by hemodynamic stress questioning the use of I -1c as a potential strategy to treat heart failure in conditions with increased afterload.
Long‐term β‐adrenergic stimulation leads to downregulation of protein phosphatase inhibitor‐1 in the heart
Role of protein phosphatase inhibitor-1 in cardiac beta adrenergic pathway.
Role of calcineurin and protein phosphatase-2A in the regulation of phosphatase inhibitor-1 in cardiac myocytes.
Role of protein phosphatase-1 inhibitor-1 in cardiac physiology and pathophysiology.
Activation of endogenous protein phosphatase 1 enhances the calcium sensitivity of the ryanodine receptor type 2 in murine ventricular cardiomyocytes
TLDR
The approach unmasks the functional importance of PP‐1 in the regulation of RyR2 activity, suggesting a potential role in the generation of a pathophysiological sarcoplasmic reticulum Ca2+ leak in the diseased heart.
Identification of a Novel Phosphorylation Site in Protein Phosphatase Inhibitor-1 as a Negative Regulator of Cardiac Function*
TLDR
Phosphorylation of inhibitor-1 at threonine 75 represents a new mechanism of cardiac contractility regulation, partially through the alteration of sarcoplasmic reticulum calcium transport activity.
Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging.
TLDR
Conditional expression of I-1c or I- 1S67A enhanced steady-state phosphorylation of 2 key Ca2+-regulating sarcoplasmic reticulum enzymes, associated with increased contractile function in young animals but also with arrhythmias and cardiomyopathy after adrenergic stress and with aging.
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References

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TLDR
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