PMID- 10617630
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 1
DP  - 2000 Jan 7
TI  - Constitutive phosphorylation of the Parkinson's disease associated
      alpha-synuclein.
PG  - 390-7
AB  - alpha-Synuclein has been implicated in the pathogenesis of Parkinson's disease,
      since rare autosomal dominant mutations are associated with early onset of the
      disease and alpha-synuclein was found to be a major constituent of Lewy bodies.
      We have analyzed alpha-synuclein expression in transfected cell lines. In
      pulse-chase experiments alpha-synuclein appeared to be stable over long periods
      (t((1)/(2)) 54 h) and no endoproteolytic processing was observed. alpha-Synuclein
      was constitutively phosphorylated in human kidney 293 cells as well as in rat
      pheochromocytoma PC12 cells. In both cell lines phosphorylation was highly
      sensitive to phosphatases, since okadaic acid markedly stabilized phosphate
      incorporation. Phosphoamino acid analysis revealed that phosphorylation occurred 
      predominantly on serine. Using site-directed mutagenesis we have identified a
      major phosphorylation site at serine 129 within the C-terminal domain of
      alpha-synuclein. An additional site, which was phosphorylated less efficiently,
      was mapped to serine 87. The major phosphorylation site was located within a
      consensus recognition sequence of casein kinase 1 (CK-1). In vitro experiments
      and two-dimensional phosphopeptide mapping provided further evidence that serine 
      129 was phosphorylated by CK-1 and CK-2. Moreover, phosphorylation of serine 129 
      was reduced in vivo upon inhibition of CK-1 or CK-2. These data demonstrate that 
      alpha-synuclein is constitutively phosphorylated within its C terminus and may
      indicate that the function of alpha-synuclein is regulated by
      phosphorylation/dephosphorylation.
FAU - Okochi, M
AU  - Okochi M
AD  - Adolf-Butenandt Institute, Department of Biochemistry, Ludwig-Maximilians
      University, 80336 Munich, Germany.
FAU - Walter, J
AU  - Walter J
FAU - Koyama, A
AU  - Koyama A
FAU - Nakajo, S
AU  - Nakajo S
FAU - Baba, M
AU  - Baba M
FAU - Iwatsubo, T
AU  - Iwatsubo T
FAU - Meijer, L
AU  - Meijer L
FAU - Kahle, P J
AU  - Kahle PJ
FAU - Haass, C
AU  - Haass C
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 (Nerve Tissue Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (SNCA protein, human)
RN  - 0 (Snca protein, rat)
RN  - 0 (Synucleins)
RN  - 0 (alpha-Synuclein)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Casein Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibody Specificity
MH  - Brain Chemistry
MH  - Casein Kinase II
MH  - Casein Kinases
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nerve Tissue Proteins/genetics/immunology/*metabolism
MH  - PC12 Cells
MH  - Parkinson Disease/*metabolism
MH  - Phosphoproteins/genetics/immunology/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors
MH  - Protein Kinases/metabolism
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Serine/genetics
MH  - Synucleins
MH  - alpha-Synuclein
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - 10.1074/jbc.275.1.390 [doi]
AID - S0021-9258(19)52877-0 [pii]
PST - ppublish
SO  - J Biol Chem. 2000 Jan 7;275(1):390-7. doi: 10.1074/jbc.275.1.390.