Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system.
Several neurological diseases, including Parkinson disease and dementia with Lewy bodies, are characterized by the accumulation of alpha-synuclein phosphorylated at Ser-129 (p-Ser-129). The kinase or kinases responsible for this phosphorylation have been the subject of intense investigation. Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons. PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay. Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo. Finally, specific knockdown of PLK2 expression by transduction with short hairpin RNA constructs or by knock-out of the plk2 gene reduced p-Ser-129 levels. These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.
Pubmed ID: 19004816 RIS Download
Animals | Base Sequence | Cell Line | Central Nervous System | DNA Primers | Enzyme-Linked Immunosorbent Assay | Humans | Mice | Mice, Inbred C57BL | Mice, Knockout | Phosphorylation | Protein Kinases | Protein-Serine-Threonine Kinases | RNA Interference | Serine | alpha-Synuclein