Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme

Akira Nakashima, Keiji Mori, Yoko S. Kaneko, Nobuhiro Hayashi, Toshiharu Nagatsu, Akira Ota

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, and its N-terminus plays a critical role in the intracellular stability of the enzyme. In the present study, we investigated the mechanism by which the N-terminal region of TH affects this stability. TH molecules phosphorylated at their Ser31 and Ser40 were localized predominantly in the cytoplasm of PC12D cells. However, those molecules phosphorylated at Ser19 were found mainly in the nucleus, whereas they seemed to be negligible in the cytoplasm. The inhibition of proteasomes increased the quantity of TH molecules phosphorylated at their Ser19 and Ser40, although it did not increase that of TH molecules or that of TH phosphorylated at its Ser31. The inhibition of autophagy did not affect the amount of the TH molecule or that of its three phosphorylated forms. Deletion mutants of human TH type-1 lacking the N-terminal region containing the three phosphorylation sites possessed high stability of the enzyme in PC12D cells. These results suggest that the phosphorylation of the N-terminal portion of TH regulates the degradation of this enzyme by the ubiquitin-proteasome pathway.

Original languageEnglish
Pages (from-to)343-347
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume407
Issue number2
DOIs
Publication statusPublished - 08-04-2011

Fingerprint

Phosphorylation
Tyrosine 3-Monooxygenase
Digestion
Enzymes
Molecules
Enzyme Stability
Proteasome Endopeptidase Complex
Cytoplasm
Biosynthesis
Autophagy
Ubiquitin
Catecholamines
Degradation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nakashima, Akira ; Mori, Keiji ; Kaneko, Yoko S. ; Hayashi, Nobuhiro ; Nagatsu, Toshiharu ; Ota, Akira. / Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 407, No. 2. pp. 343-347.
@article{caf13d63480f42128967ac789674a802,
title = "Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme",
abstract = "Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, and its N-terminus plays a critical role in the intracellular stability of the enzyme. In the present study, we investigated the mechanism by which the N-terminal region of TH affects this stability. TH molecules phosphorylated at their Ser31 and Ser40 were localized predominantly in the cytoplasm of PC12D cells. However, those molecules phosphorylated at Ser19 were found mainly in the nucleus, whereas they seemed to be negligible in the cytoplasm. The inhibition of proteasomes increased the quantity of TH molecules phosphorylated at their Ser19 and Ser40, although it did not increase that of TH molecules or that of TH phosphorylated at its Ser31. The inhibition of autophagy did not affect the amount of the TH molecule or that of its three phosphorylated forms. Deletion mutants of human TH type-1 lacking the N-terminal region containing the three phosphorylation sites possessed high stability of the enzyme in PC12D cells. These results suggest that the phosphorylation of the N-terminal portion of TH regulates the degradation of this enzyme by the ubiquitin-proteasome pathway.",
author = "Akira Nakashima and Keiji Mori and Kaneko, {Yoko S.} and Nobuhiro Hayashi and Toshiharu Nagatsu and Akira Ota",
year = "2011",
month = "4",
day = "8",
doi = "10.1016/j.bbrc.2011.03.020",
language = "English",
volume = "407",
pages = "343--347",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme. / Nakashima, Akira; Mori, Keiji; Kaneko, Yoko S.; Hayashi, Nobuhiro; Nagatsu, Toshiharu; Ota, Akira.

In: Biochemical and Biophysical Research Communications, Vol. 407, No. 2, 08.04.2011, p. 343-347.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme

AU - Nakashima, Akira

AU - Mori, Keiji

AU - Kaneko, Yoko S.

AU - Hayashi, Nobuhiro

AU - Nagatsu, Toshiharu

AU - Ota, Akira

PY - 2011/4/8

Y1 - 2011/4/8

N2 - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, and its N-terminus plays a critical role in the intracellular stability of the enzyme. In the present study, we investigated the mechanism by which the N-terminal region of TH affects this stability. TH molecules phosphorylated at their Ser31 and Ser40 were localized predominantly in the cytoplasm of PC12D cells. However, those molecules phosphorylated at Ser19 were found mainly in the nucleus, whereas they seemed to be negligible in the cytoplasm. The inhibition of proteasomes increased the quantity of TH molecules phosphorylated at their Ser19 and Ser40, although it did not increase that of TH molecules or that of TH phosphorylated at its Ser31. The inhibition of autophagy did not affect the amount of the TH molecule or that of its three phosphorylated forms. Deletion mutants of human TH type-1 lacking the N-terminal region containing the three phosphorylation sites possessed high stability of the enzyme in PC12D cells. These results suggest that the phosphorylation of the N-terminal portion of TH regulates the degradation of this enzyme by the ubiquitin-proteasome pathway.

AB - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, and its N-terminus plays a critical role in the intracellular stability of the enzyme. In the present study, we investigated the mechanism by which the N-terminal region of TH affects this stability. TH molecules phosphorylated at their Ser31 and Ser40 were localized predominantly in the cytoplasm of PC12D cells. However, those molecules phosphorylated at Ser19 were found mainly in the nucleus, whereas they seemed to be negligible in the cytoplasm. The inhibition of proteasomes increased the quantity of TH molecules phosphorylated at their Ser19 and Ser40, although it did not increase that of TH molecules or that of TH phosphorylated at its Ser31. The inhibition of autophagy did not affect the amount of the TH molecule or that of its three phosphorylated forms. Deletion mutants of human TH type-1 lacking the N-terminal region containing the three phosphorylation sites possessed high stability of the enzyme in PC12D cells. These results suggest that the phosphorylation of the N-terminal portion of TH regulates the degradation of this enzyme by the ubiquitin-proteasome pathway.

UR - http://www.scopus.com/inward/record.url?scp=79953729317&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953729317&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2011.03.020

DO - 10.1016/j.bbrc.2011.03.020

M3 - Article

C2 - 21392500

AN - SCOPUS:79953729317

VL - 407

SP - 343

EP - 347

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -