title: Protein kinase C-dependent dephosphorylation of tyrosine hydroxylase requires the B56δ heterotrimeric form of protein phosphatase 2A.
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.
authors: Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea.
authors: Jung-Hyuck
authors: JH
authors: Ahn
authors: Yong
authors: Y
authors: Kim
authors: Hee-Sun
authors: HS
authors: Kim
authors: Paul
authors: P
authors: Greengard
authors: Angus C
authors: AC
authors: Nairn
mesh_terms: D000818:Animals; D002460:Cell Line; D004298:Dopamine / Q000096:biosynthesis; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000378:metabolism*; D021122:Protein Subunits; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D054648:Protein Phosphatase 2; D004298:Dopamine