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The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human

Elena J Kumm1, Oliver Pagel2, Stepan Gambaryan1,3

  • 1Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

Cells
|February 23, 2020
PubMed

Insights

The MASTL-ENSA/ARPP19-PP2A pathway regulates platelet function. This study identifies this cell cycle pathway in human platelets, impacting aggregation and kinase signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Hematology

Background:

  • The cell cycle is regulated by MASTL kinase, which influences PP2A activity via ENSA/ARPP19.
  • The MASTL-ENSA/ARPP19-PP2A pathway's role in platelets was previously unknown.

Purpose of the Study:

  • To investigate the presence and function of the MASTL-ENSA/ARPP19-PP2A pathway in human platelets.
  • To explore the pathway's interactions with other signaling systems in platelets.

Main Methods:

  • Proteomic analysis of human platelets to detect pathway components.
  • In vitro phosphorylation and dephosphorylation assays using recombinant proteins.
  • Pharmacological inhibition of PP2A and assessment of platelet aggregation and kinase activity.

Main Results:

  • ENSA, ARPP19, and PP2A subunits were identified in human platelets.
  • Phosphorylation of ENSA/ARPP19 was observed upon cAMP/cGMP elevation and PP2A inhibition.
  • PP2A inhibition reduced platelet aggregation and altered VASP, Akt, and MAPK phosphorylation.

Conclusions:

  • The complete MASTL(like)-ENSA/ARPP19-PP2A signaling pathway is present and functional in human platelets.
  • This pathway interacts with PKA, MAPK, and PI3K/Akt signaling systems.
  • The pathway plays a role in regulating platelet aggregation and kinase signaling.
Keywords:
ARPP19ENSAMAP kinasecyclic AMPcyclic GMPplateletsserine/threonine protein phosphatases

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