Musante2017 - Switching behaviour of PP2A inhibition by ARPP-16 - mutual inhibitions and PKA inhibits MAST3

Model Identifier
BIOMD0000000644
Short description
Musante2017 - Switching behaviour of PP2A inhibition by ARPP-16 - mutual inhibitions and PKA inhibits MAST3

This model is described in the article:

Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition.
Musante V, Li L, Kanyo J, Lam TT, Colangelo CM, Cheng SK, Brody AH, Greengard P, Le Novère N, Nairn AC.
Elife 2017 Jun; 6:

Abstract:

ARPP-16, ARPP-19, and ENSA are inhibitors of protein phosphatase PP2A. ARPP-19 and ENSA phosphorylated by Greatwall kinase inhibit PP2A during mitosis. ARPP-16 is expressed in striatal neurons where basal phosphorylation by MAST3 kinase inhibits PP2A and regulates key components of striatal signaling. The ARPP-16/19 proteins were discovered as substrates for PKA, but the function of PKA phosphorylation is unknown. We find that phosphorylation by PKA or MAST3 mutually suppresses the ability of the other kinase to act on ARPP-16. Phosphorylation by PKA also acts to prevent inhibition of PP2A by ARPP-16 phosphorylated by MAST3. Moreover, PKA phosphorylates MAST3 at multiple sites resulting in its inhibition. Mathematical modeling highlights the role of these three regulatory interactions to create a switch-like response to cAMP. Together, the results suggest a complex antagonistic interplay between the control of ARPP-16 by MAST3 and PKA that creates a mechanism whereby cAMP mediates PP2A disinhibition.

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To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.

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Format
SBML (L3V1)
Related Publication
  • Reciprocal regulation of ARPP-16 by PKA and MAST-3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition
  • Veronica Musante, Lu Li, Jean Kanyo, Tukiet T Lam, Christopher M Colangelo, Shuk Kei Cheng, Harrison Brody, Paul Greengard, Nicolas Le Novère, Angus C Nairn
  • eLIFE , 9/ 2017 , DOI: 10.7554/eLife.24998
Contributors
Submitter of the first revision: Lu Li
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modellers: administrator, Lu Li

Metadata information

is (2 statements)
BioModels Database BIOMD0000000644
BioModels Database MODEL1707020001

hasTaxon (1 statement)
Taxonomy Mus sp.

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

isDerivedFrom (1 statement)
Brenda Tissue Ontology HEK-293T cell

isDescribedBy (2 statements)
Curation status
Curated
Modelling approach(es)
ordinary differential equation model

Connected external resources