Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.

Polycystin signaling is likely to be regulated by phosphorylation. While a number of potential protein kinases and their target phosphorylation sites on polycystin-1 have been identified, the corresponding phosphatases have not been extensively studied. We have now determined that polycystin-1 is a...

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Main Authors: Stephen C Parnell, Sanjeev Puri, Darren P Wallace, James P Calvet
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3366979?pdf=render
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spelling doaj-a632d16e7ef94a6f91130072306b51b82020-11-25T01:46:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3679810.1371/journal.pone.0036798Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.Stephen C ParnellSanjeev PuriDarren P WallaceJames P CalvetPolycystin signaling is likely to be regulated by phosphorylation. While a number of potential protein kinases and their target phosphorylation sites on polycystin-1 have been identified, the corresponding phosphatases have not been extensively studied. We have now determined that polycystin-1 is a regulatory subunit for protein phosphatase-1α (PP1α). Sequence analysis has revealed the presence of a highly conserved PP1-interaction motif in the cytosolic, C-terminal tail of polycystin-1; and we have shown that transfected PP1α specifically co-immunoprecipitates with a polycystin-1 C-tail construct. To determine whether PP1α dephosphorylates polycystin-1, a PKA-phosphorylated GST-polycystin-1 fusion protein was shown to be dephosphorylated by PP1α but not by PP2B (calcineurin). Mutations within the PP1-binding motif of polycystin-1, including an autosomal dominant polycystic kidney disease (ADPKD)-associated mutation, significantly reduced PP1α-mediated dephosphorylation of polycystin-1. The results suggest that polycystin-1 forms a holoenzyme complex with PP1α via a conserved PP1-binding motif within the polycystin-1 C-tail, and that PKA-phosphorylated polycystin-1 serves as a substrate for the holoenzyme.http://europepmc.org/articles/PMC3366979?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Stephen C Parnell
Sanjeev Puri
Darren P Wallace
James P Calvet
spellingShingle Stephen C Parnell
Sanjeev Puri
Darren P Wallace
James P Calvet
Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
PLoS ONE
author_facet Stephen C Parnell
Sanjeev Puri
Darren P Wallace
James P Calvet
author_sort Stephen C Parnell
title Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
title_short Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
title_full Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
title_fullStr Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
title_full_unstemmed Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
title_sort protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description Polycystin signaling is likely to be regulated by phosphorylation. While a number of potential protein kinases and their target phosphorylation sites on polycystin-1 have been identified, the corresponding phosphatases have not been extensively studied. We have now determined that polycystin-1 is a regulatory subunit for protein phosphatase-1α (PP1α). Sequence analysis has revealed the presence of a highly conserved PP1-interaction motif in the cytosolic, C-terminal tail of polycystin-1; and we have shown that transfected PP1α specifically co-immunoprecipitates with a polycystin-1 C-tail construct. To determine whether PP1α dephosphorylates polycystin-1, a PKA-phosphorylated GST-polycystin-1 fusion protein was shown to be dephosphorylated by PP1α but not by PP2B (calcineurin). Mutations within the PP1-binding motif of polycystin-1, including an autosomal dominant polycystic kidney disease (ADPKD)-associated mutation, significantly reduced PP1α-mediated dephosphorylation of polycystin-1. The results suggest that polycystin-1 forms a holoenzyme complex with PP1α via a conserved PP1-binding motif within the polycystin-1 C-tail, and that PKA-phosphorylated polycystin-1 serves as a substrate for the holoenzyme.
url http://europepmc.org/articles/PMC3366979?pdf=render
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