Musante2017 - Switching behaviour of PP2A inhibition by ARPP-16 - mutual inhibitions

Musante2017 - Switching behaviour of PP2A
inhibition by ARPP-16 - mutual inhibitions

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.

This model is hosted on
BioModels Database
and identified by:
BIOMD0000000643.
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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