Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of catecholamines: Evidence for a novel regulatory mechanism

Andrew J. Ramsey, Paul F Fitzpatrick

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The effects of phosphorylation at Ser40 of rat tyrosine hydroxylase on the affinities of catechols have been determined with both the ferric and ferrous forms of the enzyme. Phosphorylation had no effect on the K(i) value for the inhibition of the ferrous enzyme by either dopamine or DOPA when the initial rate of turnover was measured in assays. However, phosphorylation of the ferric enzyme resulted in a 17-fold decrease in affinity for DOPA and a 300-fold decrease in the affinity for dopamine, while the affinity for dihydroxynaphthalene was unchanged. The changes in binding affinity for the two catecholamines were almost exclusively due to large increases in the dissociation rate constants upon phosphorylation. These results support a novel mechanism for regulation in which phosphorylation affects binding of catecholamines to the catalytically inactive ferric form of the tyrosine hydroxylase.

Original languageEnglish (US)
Pages (from-to)8980-8986
Number of pages7
JournalBiochemistry
Volume37
Issue number25
DOIs
StatePublished - Jun 23 1998
Externally publishedYes

Fingerprint

Phosphorylation
Tyrosine 3-Monooxygenase
Serine
Catecholamines
Dopamine
Enzymes
Catechols
Rats
Rate constants
Assays

ASJC Scopus subject areas

  • Biochemistry

Cite this

Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of catecholamines : Evidence for a novel regulatory mechanism. / Ramsey, Andrew J.; Fitzpatrick, Paul F.

In: Biochemistry, Vol. 37, No. 25, 23.06.1998, p. 8980-8986.

Research output: Contribution to journalArticle

@article{7cd7ce3334424afe806402c33e567196,
title = "Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of catecholamines: Evidence for a novel regulatory mechanism",
abstract = "The effects of phosphorylation at Ser40 of rat tyrosine hydroxylase on the affinities of catechols have been determined with both the ferric and ferrous forms of the enzyme. Phosphorylation had no effect on the K(i) value for the inhibition of the ferrous enzyme by either dopamine or DOPA when the initial rate of turnover was measured in assays. However, phosphorylation of the ferric enzyme resulted in a 17-fold decrease in affinity for DOPA and a 300-fold decrease in the affinity for dopamine, while the affinity for dihydroxynaphthalene was unchanged. The changes in binding affinity for the two catecholamines were almost exclusively due to large increases in the dissociation rate constants upon phosphorylation. These results support a novel mechanism for regulation in which phosphorylation affects binding of catecholamines to the catalytically inactive ferric form of the tyrosine hydroxylase.",
author = "Ramsey, {Andrew J.} and Fitzpatrick, {Paul F}",
year = "1998",
month = "6",
day = "23",
doi = "10.1021/bi980582l",
language = "English (US)",
volume = "37",
pages = "8980--8986",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "25",

}

TY - JOUR

T1 - Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of catecholamines

T2 - Evidence for a novel regulatory mechanism

AU - Ramsey, Andrew J.

AU - Fitzpatrick, Paul F

PY - 1998/6/23

Y1 - 1998/6/23

N2 - The effects of phosphorylation at Ser40 of rat tyrosine hydroxylase on the affinities of catechols have been determined with both the ferric and ferrous forms of the enzyme. Phosphorylation had no effect on the K(i) value for the inhibition of the ferrous enzyme by either dopamine or DOPA when the initial rate of turnover was measured in assays. However, phosphorylation of the ferric enzyme resulted in a 17-fold decrease in affinity for DOPA and a 300-fold decrease in the affinity for dopamine, while the affinity for dihydroxynaphthalene was unchanged. The changes in binding affinity for the two catecholamines were almost exclusively due to large increases in the dissociation rate constants upon phosphorylation. These results support a novel mechanism for regulation in which phosphorylation affects binding of catecholamines to the catalytically inactive ferric form of the tyrosine hydroxylase.

AB - The effects of phosphorylation at Ser40 of rat tyrosine hydroxylase on the affinities of catechols have been determined with both the ferric and ferrous forms of the enzyme. Phosphorylation had no effect on the K(i) value for the inhibition of the ferrous enzyme by either dopamine or DOPA when the initial rate of turnover was measured in assays. However, phosphorylation of the ferric enzyme resulted in a 17-fold decrease in affinity for DOPA and a 300-fold decrease in the affinity for dopamine, while the affinity for dihydroxynaphthalene was unchanged. The changes in binding affinity for the two catecholamines were almost exclusively due to large increases in the dissociation rate constants upon phosphorylation. These results support a novel mechanism for regulation in which phosphorylation affects binding of catecholamines to the catalytically inactive ferric form of the tyrosine hydroxylase.

UR - http://www.scopus.com/inward/record.url?scp=0032560609&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032560609&partnerID=8YFLogxK

U2 - 10.1021/bi980582l

DO - 10.1021/bi980582l

M3 - Article

C2 - 9636040

AN - SCOPUS:0032560609

VL - 37

SP - 8980

EP - 8986

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 25

ER -