Document Detail


Role of serine-19 phosphorylation in regulating tyrosine hydroxylase studied with site- and phosphospecific antibodies and site-directed mutagenesis.
MedLine Citation:
PMID:  9751201     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of depolarization by elevated potassium concentrations were studied in PC12 cells and in stably transfected AtT-20 cells expressing wild-type or [Leu19]-recombinant tyrosine hydroxylase (rTH). Changes in the phosphorylation states of Ser19 and Ser40 in tyrosine hydroxylase (TH) were determined immunochemically using antibodies specific for the phosphorylated state of each site and compared with changes in TH activity in PC12 cell lysates and with changes in L-DOPA biosynthesis rates in intact AtT-20 cells. Treatment of either PC12 cells or AtT-20 cells expressing wild-type rTH with elevated potassium produced a transient increase in the phosphorylation state of Ser19 (up to 0.7 mol of phosphate/mol of subunit) in concert with a more gradual and sustained increase in Ser40 phosphorylation. Elevated potassium treatment also increased TH activity in PC12 cell lysates, but these increases paralleled the temporal course of Ser40, as opposed to Ser19, phosphorylation. Similarly, increases in DOPA accumulation produced by elevated potassium in AtT-20 cells expressing wild-type rTH paralleled the increases in the phosphorylation state of Ser40 but not Ser19. Moreover, elevated potassium produced comparable increases in DOPA accumulation in AtT-20 cells expressing rTH in which Ser19 phosphorylation had been eliminated (by substitution of Leu for Ser19). Thus, depolarization-induced increases in the stoichiometry of Ser19 phosphorylation do not appear to influence directly the activity of TH in situ.
Authors:
J W Haycock; J Y Lew; A Garcia-Espana; K Y Lee; K Harada; E Meller; M Goldstein
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  71     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-10-14     Completed Date:  1998-10-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1670-5     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70119, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution / genetics
Animals
Antibody Specificity*
Cell Line
Enzyme Activation / drug effects
Mice
Mutagenesis, Site-Directed*
PC12 Cells / drug effects
Phosphates / immunology,  metabolism*
Phosphorylation / drug effects
Potassium / metabolism
Rats
Recombinant Proteins / biosynthesis
Serine / genetics,  metabolism*
Tyrosine 3-Monooxygenase / chemistry,  genetics*,  metabolism*
Grant Support
ID/Acronym/Agency:
MH02717/MH/NIMH NIH HHS; NS06801/NS/NINDS NIH HHS; NS25134/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Phosphates; 0/Recombinant Proteins; 56-45-1/Serine; 7440-09-7/Potassium; EC 1.14.16.2/Tyrosine 3-Monooxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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