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Protein kinase C-dependent dephosphorylation of tyrosine hydroxylase requires the B56δ heterotrimeric form of protein phosphatase 2A
- Title
- Protein kinase C-dependent dephosphorylation of tyrosine hydroxylase requires the B56δ heterotrimeric form of protein phosphatase 2A
- Authors
- Ahn J.-H.; Kim Y.; Kim H.-S.; Greengard P.; Nairn A.C.
- Ewha Authors
- 김희선; 안정혁
- SCOPUS Author ID
- 김희선; 안정혁
- Issue Date
- 2011
- Journal Title
- PLoS ONE
- ISSN
- 1932-6203
- Citation
- PLoS ONE vol. 6, no. 10
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Tyrosine hydroxylase, which plays a critical role in regulation of dopamine synthesis, is known to be controlled by phosphorylation at several critical sites. One of these sites, Ser40, is phosphorylated by a number of protein kinases, including protein kinase A. The major protein phosphatase that dephosphorylates Ser40 is protein phosphatase-2A (PP2A). A recent study has also linked protein kinase C to the dephosphorylation of Ser40 [1] but the mechanism is unclear. PP2A isoforms are comprised of catalytic, scaffold, and regulatory subunits, the regulatory B subunits being able to influence cellular localization and substrate selection. In the current study, we find that protein kinase C is able to phosphorylate a key regulatory site in the B56δ subunit leading to activation of PP2A. In turn, activation of the B56δ-containing heterotrimeric form of PP2A is responsible for enhanced dephosphorylation of Ser40 of tyrosine hydroylase in response to stimulation of PKC. In support of this mechanism, down-regulation of B56δ expression in N27 cells using RNAi was found to increase dopamine synthesis. Together these studies reveal molecular details of how protein kinase C is linked to reduced tyrosine hydroxylase activity via control of PP2A, and also add to the complexity of protein kinase/protein phosphatase interactions. © 2011 Ahn et al.
- DOI
- 10.1371/journal.pone.0026292
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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