ArticleThe Journal of biological chemistry2010
Phosphorylation of synucleins by members of the Polo-like kinase family.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 1 of them a synthesis that pooled it.
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Who cites it
148 citing papers in PubMed, 1 synthesis or guideline pooled it, 245 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Article
- Imaging spatial transcriptomics reveals molecular patterns underlying accumulation of p-Ser129 α-synuclein in a transgenic mouse model.NPJ Parkinson's disease · 2026Article
- Alpha-Synuclein Dynamics in Cerebral Ischemia.ASN neuro · 2026Review
- Tau protein in Parkinson's disease: advances in phosphoproteomics and molecular dynamics simulations.Frontiers in aging neuroscience · 2026Review
- Synuclein Proteoforms: Role in Health and Disease.Molecular neurobiology · 2025Review
- Article
- Infection and herbicide exposure implicate c-Abl kinase in α-Synuclein Ser129 phosphorylation.Cell communication and signaling : CCS · 2025Article
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- Structural and functional insights into the nuclear role of Parkinson's disease-associated α-synuclein as a histone chaperone.Communications biology · 2025Article
- Molecular Determinants of Protein Pathogenicity at the Single-Aggregate Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- α-Synuclein orchestrates Th17 responses as antigen and adjuvant in Parkinson's disease.Journal of neuroinflammation · 2025Article
- Novel tools to quantify total, phospho-Ser129 and aggregated alpha-synuclein in the mouse brain.NPJ Parkinson's disease · 2024Article
- Article
- PLK2-mediated phosphorylation of SQSTM1 S349 promotes aggregation of polyubiquitinated proteins upon proteasomal dysfunction.Autophagy · 2024Article
- The role of polo-like kinases 2 in the proteasomal and lysosomal degradation of alpha-synuclein in neurons.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Article
- RXR nuclear receptor signaling modulates lipid metabolism and triggers lysosomal clearance of alpha-synuclein in neuronal models of synucleinopathy.Cellular and molecular life sciences : CMLS · 2024Article
- Article
88 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphorylation of alpha-synuclein (alpha-syn) at Ser-129 is a hallmark of Parkinson disease and related synucleinopathies. However, the identity of the natural kinases and phosphatases responsible for regulating alpha-syn phosphorylation remain unknown. Here we demonstrate that three closely related members of the human Polo-like kinase (PLK) family (PLK1, PLK2, and PLK3) phosphorylate alpha-syn and beta-syn specifically at Ser-129 and Ser-118, respectively. Unlike other kinases reported to partially phosphorylate alpha-syn at Ser-129 in vitro, phosphorylation by PLK2 and PLK3 is quantitative (>95% conversion). Only PLK1 and PLK3 phosphorylate beta-syn at Ser-118, whereas no phosphorylation of gamma-syn was detected by any of the four PLKs (PLK1 to -4). PLK-mediated phosphorylation was greatly reduced in an isolated C-terminal fragment (residues 103-140) of alpha-syn, suggesting substrate recognition via the N-terminal repeats and/or the non-amyloid component domain of alpha-syn. PLKs specifically co-localized with phosphorylated Ser-129 (Ser(P)-129) alpha-syn in various subcellular compartments (cytoplasm, nucleus, and membranes) of mammalian cell lines and primary neurons as well as in alpha-syn transgenic mice, especially cortical brain areas involved in synaptic plasticity. Furthermore, we report that the levels of PLK2 are significantly increased in brains of Alzheimer disease and Lewy body disease patients. Taken together, these results provide biochemical and in vivo evidence of alpha-syn and beta-syn phosphorylation by specific PLKs. Our results suggest a need for further studies to elucidate the potential role of PLK-syn interactions in the normal biology of these proteins as well as their involvement in the pathogenesis of Parkinson disease and other synucleinopathies.
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