PMID- 10531334
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 44
DP  - 1999 Oct 29
TI  - Serine 19 of human 6-pyruvoyltetrahydropterin synthase is phosphorylated by cGMP 
      protein kinase II.
PG  - 31341-8
AB  - 6-Pyruvoyltetrahydropterin synthase (PTPS) participates in tetrahydrobiopterin
      cofactor biosynthesis. We previously identified in a PTPS-deficient patient an
      inactive PTPS allele with an Arg(16) to Cys codon mutation. Arg(16) is located in
      the protein surface exposed phosphorylation motif Arg(16)-Arg-Ile-Ser, with
      Ser(19) as the putative phosphorylation site for serine-threonine protein
      kinases. Purification of recombinant PTPS-S19A from bacterial cells resulted in
      an active enzyme (k(cat)/K(m) = 6.4 x 10(3) M(-1) s(-1)), which was similar to
      wild-type PTPS (k(cat)/K(m) = 4.1 x 10(3) M(-1) s(-1)). In assays with purified
      enzymes, wild-type but not PTPS-S19A was a specific substrate for the
      cGMP-dependent protein kinase (cGK) type I and II. Upon expression in COS-1
      cells, PTPS-S19A was stable but not phosphorylated and had a reduced activity of 
      approximately 33% in comparison to wild-type PTPS. Extracts from several human
      cell lines, including brain, contained a kinase that bound to and phosphorylated 
      immobilized wild-type, but not mutant PTPS. Addition of cGMP stimulated
      phosphotransferase activity 2-fold. Extracts from transfected COS-1 cells
      overexpressing cGKII stimulated Ser(19) phosphorylation more than 100-fold, but
      only 4-fold from cGKI overexpressing cells. Moreover, fibroblast extracts from
      mice lacking cGKII exhibited significantly reduced phosphorylation of PTPS. These
      results suggest that Ser(19) of human PTPS may be a substrate for cGKII
      phosphorylation also in vivo, a modification that is essential for normal
      activity.
FAU - Scherer-Oppliger, T
AU  - Scherer-Oppliger T
AD  - Department of Pediatrics, Division of Clinical Chemistry and Biochemistry,
      University of Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.
FAU - Leimbacher, W
AU  - Leimbacher W
FAU - Blau, N
AU  - Blau N
FAU - Thony, B
AU  - Thony B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Alkaloids)
RN  - 0 (Carbazoles)
RN  - 0 (Indoles)
RN  - 0 (Recombinant Proteins)
RN  - 126643-37-6 (KT 5823)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinase Type II)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
RN  - EC 2.7.11.12 (PRKG2 protein, human)
RN  - EC 2.7.11.12 (Prkg2 protein, mouse)
RN  - EC 4.6.- (Phosphorus-Oxygen Lyases)
RN  - EC 4.6.10 (6-pyruvoyltetrahydropterin synthase)
RN  - H88EPA0A3N (Staurosporine)
SB  - IM
MH  - Alkaloids/pharmacology
MH  - Amino Acid Metabolism, Inborn Errors/enzymology/*genetics
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - *Carbazoles
MH  - Consensus Sequence
MH  - Cyclic GMP-Dependent Protein Kinase Type II
MH  - Cyclic GMP-Dependent Protein Kinases/antagonists &
      inhibitors/genetics/*metabolism
MH  - Fibroblasts/enzymology
MH  - Humans
MH  - *Indoles
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphorus-Oxygen Lyases/deficiency/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases
MH  - Recombinant Proteins/metabolism
MH  - Serine/*metabolism
MH  - Skin/enzymology
MH  - Staurosporine/pharmacology
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1074/jbc.274.44.31341 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 29;274(44):31341-8. doi: 10.1074/jbc.274.44.31341.