title: Superiority of PLK-2 as α-synuclein phosphorylating agent relies on unique specificity determinants.
abstract: Phosphorylation of α-synuclein at Ser-129 is of crucial relevance to Parkinson's disease and related synucleinopathies. Here we provide biochemical evidence that PLK2 and to a lesser extent PLK3 are superior over CK2, as catalysts of Ser-129 phosphorylation both in full length α-synuclein and in a peptide reproducing the C-terminal segment of the protein. By using substituted peptides we also show that the sequence surrounding Ser-129 is optimally shaped for undergoing phosphorylation by PLK2, with special reference to the two acidic residues at positions n-3 (Glu-126) and n+2 (Glu-131) whose replacement with alanine abrogates phosphorylation.
authors.affiliation: Department of Biological Chemistry and CNR Institute of Neurosciences, University of Padova, V.le G. Colombo 3, 35131 Padova, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Salvi
authors.forename: Edlir
authors.initials: E
authors.lastname: Trashi
authors.forename: Oriano
authors.initials: O
authors.lastname: Marin
authors.forename: Alessandro
authors.initials: A
authors.lastname: Negro
authors.forename: Stefania
authors.initials: S
authors.lastname: Sarno
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Pinna
mesh_terms: D047390:Casein Kinase II / Q000378:metabolism; D002384:Catalysis; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000097868:Polo-like Kinases
chemical_list: D047390:Casein Kinase II; D010455:Peptides; D017346:Protein Serine-Threonine Kinases; D012694:Serine; D025521:Tumor Suppressor Proteins; D051844:alpha-Synuclein; C486256:PLK3 protein, human; D000097868:Polo-like Kinases; C496126:PLK2 protein, human