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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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 |
work_keys_str_mv |
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