Multiple phosphorylation of α-synuclein by protein tyrosine kinase Syk prevents eosin-induced aggregation

摘要: The presence of aggregated alpha-synuclein molecules is a common denominator in variety neurodegenerative disorders. Here, we show that (alpha-syn) an outstanding substrate for the protein tyrosine kinase p72syk (Syk), which phosphorylates three tyrosyl residues its C-terminal domain (Y-125, Y-133, and Y-136), as revealed from experiments with mutants where these have been individually or multiply replaced by phenylalanine. In contrast, only Y-125 phosphorylated Lyn c-Fgr. Eosin-induced multimerization observed wild-type alpha-syn, either not Lyn, all Tyr to Phe but previously Syk. Syk-mediated phosphorylation also counteracts alpha-syn assembly into filaments judged disappearance precipitated upon centrifugation at 100,000 x g. We Syk colocalize brain, cotransfection Chinese hamster ovary cells, becomes Tyr-phosphorylated Moreover, interact each other mammalian two-hybrid system approach. These data suggest kinase(s) similar specificity may play antineurodegenerative role phosphorylating a-syn, thereby preventing aggregation.