PubMed Journals: J Biol Chem
Source: PMID: 11502746
⇦ ⇨ J Biol Chem. 2001 Nov 2;276(44):40411-6.
⇩ Epub 2001 Aug 13.
Phosphorylation of Ser(19) alters the conformation
of tyrosine hydroxylase to increase the
rate of phosphorylation of Ser(40).
Bevilaqua LR(1), Graham ME, Dunkley PR,
von Nagy-Felsobuki EI, Dickson PW.
(1) School of Biomedical Sciences, Faculty
of Medicine and Health Sciences, The University
of Newcastle, Callaghan, New South Wales
The effect of phosphorylation on the shape
of tyrosine hydroxylase (TH) was studied
directly using gel filtration and indirectly
using electrospray ionization mass spectrometry.
Phosphorylation of Ser(19) and Ser(40) produced
a TH molecule with a more open conformation
than the non-phosphorylated form. The conformational
effect of Ser(19) phosphorylation is less
pronounced than that of the Ser(40) phosphorylation.
The effect of Ser(19) and Ser(40) phosphorylation
appears to be additive. Binding of dopamine
produced a more compact form when compared
with the non-dopamine-bound TH. The interdependence
of Ser(19) and Ser(40) phosphorylation was
probed using electrospray ionization mass
spectrometry. The rate constants for the
phosphorylation of Ser(19) and Ser(40) were
determined by electrospray ionization mass spectrometry
using a consecutive reaction model. The
rate constant for the phosphorylation of
Ser(40) is approximately 2- to 3-fold higher
if Ser(19) is already phosphorylated. These
results suggest that phosphorylation of
Ser(19) alters the conformation of tyrosine
hydroxylase to allow increased accessibility
of Ser(40) to kinases.
DOI: 10.1074/jbc.M105280200 PMID: 11502746
[Indexed for MEDLINE]