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			PubMed Journals: J Biol Chem

  Source:		PMID: 10617630


    		J Biol Chem. 2000 Jan 7;275(1):390-7.
     
			Constitutive phosphorylation of the Parkinson's
			disease associated alpha-synuclein.

			Okochi M(1), Walter J, Koyama A, Nakajo
			S, Baba M, Iwatsubo T, Meijer L, Kahle PJ,
			Haass C.

			Author Information
			(1) Adolf-Butenandt Institute, Department
			of Biochemistry, Ludwig-Maximilians University,
			80336 Munich, Germany.

			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.

			PMID: 10617630 [Indexed for MEDLINE]

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