Article
Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function.
Proceedings of the National Academy of Sciences of the United States of America - 21 Sept 2010
Ko Han Seok, Lee Yunjong, Shin Joo-Ho, Karuppagounder Senthilkumar S, Gadad Bharathi Shrikanth, Koleske Anthony J, Pletnikova Olga, Troncoso Juan C, Dawson Valina L, Dawson Ted M
Abstract excerpt
Mutations in PARK2/Parkin, which encodes a ubiquitin E3 ligase, cause autosomal recessive Parkinson disease (PD). Here we show that the nonreceptor tyrosine kinase c-Abl phosphorylates tyrosine 143 of parkin, inhibiting parkin's ubiquitin E3 ligase activity and protective function. c-Abl is activated by dopaminergic stress and by dopaminergic neurotoxins, 1-methyl-4-phenylpyridinium (MPP(+)) in vitro and in vivo...
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