Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies - PubMed (original) (raw)

. 2007 Oct 2;581(24):4711-7.

doi: 10.1016/j.febslet.2007.08.067. Epub 2007 Sep 6.

Affiliations

• PMID: 17868672
• DOI: 10.1016/j.febslet.2007.08.067

Free article

Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies

Aasami Ishii et al. FEBS Lett. 2007.

Free article

Abstract

In Lewy body diseases and multiple system atrophy, alpha-synuclein is hyperphosphorylated at Ser129, suggesting a role in pathogenesis. Here, we report purification of the protein kinase in rat brain that phosphorylates Ser129 and its identification as casein kinase-2 (CK2). We show that most of the activity can be inhibited by heparin, an inhibitor of CK2. Phosphorylated Ser129 was detected in primary cultured neurons and inhibited by CK2 inhibitors. In some cases of Lewy body disease, CK2-like immunoreactivity was recovered in the sarkosyl-insoluble fraction, which was enriched in phosphorylated alpha-synuclein. Taken together, these findings suggest that CK2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies.

PubMed Disclaimer

Similar articles

• Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein.
  Waxman EA, Giasson BI. Waxman EA, et al. J Neuropathol Exp Neurol. 2008 May;67(5):402-16. doi: 10.1097/NEN.0b013e31816fc995. J Neuropathol Exp Neurol. 2008. PMID: 18451726 Free PMC article.
• Authentically phosphorylated α-synuclein at Ser129 accelerates neurodegeneration in a rat model of familial Parkinson's disease.
  Sato H, Arawaka S, Hara S, Fukushima S, Koga K, Koyama S, Kato T. Sato H, et al. J Neurosci. 2011 Nov 16;31(46):16884-94. doi: 10.1523/JNEUROSCI.3967-11.2011. J Neurosci. 2011. PMID: 22090514 Free PMC article.
• Novel antibodies to phosphorylated α-synuclein serine 129 and NFL serine 473 demonstrate the close molecular homology of these epitopes.
  Rutherford NJ, Brooks M, Giasson BI. Rutherford NJ, et al. Acta Neuropathol Commun. 2016 Aug 8;4(1):80. doi: 10.1186/s40478-016-0357-9. Acta Neuropathol Commun. 2016. PMID: 27503460 Free PMC article.
• Distinct α-Synuclein strains and implications for heterogeneity among α-Synucleinopathies.
  Peng C, Gathagan RJ, Lee VM. Peng C, et al. Neurobiol Dis. 2018 Jan;109(Pt B):209-218. doi: 10.1016/j.nbd.2017.07.018. Epub 2017 Jul 24. Neurobiol Dis. 2018. PMID: 28751258 Free PMC article. Review.
• α-Synuclein phosphorylation as a therapeutic target in Parkinson's disease.
  Braithwaite SP, Stock JB, Mouradian MM. Braithwaite SP, et al. Rev Neurosci. 2012 Mar 21;23(2):191-8. doi: 10.1515/revneuro-2011-0067. Rev Neurosci. 2012. PMID: 22499677 Review.

Cited by

• Proteolytic α-Synuclein Cleavage in Health and Disease.
  Bluhm A, Schrempel S, von Hörsten S, Schulze A, Roßner S. Bluhm A, et al. Int J Mol Sci. 2021 May 21;22(11):5450. doi: 10.3390/ijms22115450. Int J Mol Sci. 2021. PMID: 34064208 Free PMC article. Review.
• Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism: preclinical Parkinson disease.
  Ferrer I, Martinez A, Blanco R, Dalfó E, Carmona M. Ferrer I, et al. J Neural Transm (Vienna). 2011 May;118(5):821-39. doi: 10.1007/s00702-010-0482-8. Epub 2010 Sep 23. J Neural Transm (Vienna). 2011. PMID: 20862500 Review.
• The novel Parkinson's disease linked mutation G51D attenuates in vitro aggregation and membrane binding of α-synuclein, and enhances its secretion and nuclear localization in cells.
  Fares MB, Ait-Bouziad N, Dikiy I, Mbefo MK, Jovičić A, Kiely A, Holton JL, Lee SJ, Gitler AD, Eliezer D, Lashuel HA. Fares MB, et al. Hum Mol Genet. 2014 Sep 1;23(17):4491-509. doi: 10.1093/hmg/ddu165. Epub 2014 Apr 11. Hum Mol Genet. 2014. PMID: 24728187 Free PMC article.
• The role of polo-like kinases 2 in the proteasomal and lysosomal degradation of alpha-synuclein in neurons.
  Sung CC, Lam WY, Chung KKK. Sung CC, et al. FASEB J. 2024 Oct;38(20):e70121. doi: 10.1096/fj.202401035R. FASEB J. 2024. PMID: 39436202 Free PMC article.
• Serine 129 phosphorylation reduces the ability of alpha-synuclein to regulate tyrosine hydroxylase and protein phosphatase 2A in vitro and in vivo.
  Lou H, Montoya SE, Alerte TN, Wang J, Wu J, Peng X, Hong CS, Friedrich EE, Mader SA, Pedersen CJ, Marcus BS, McCormack AL, Di Monte DA, Daubner SC, Perez RG. Lou H, et al. J Biol Chem. 2010 Jun 4;285(23):17648-61. doi: 10.1074/jbc.M110.100867. Epub 2010 Mar 31. J Biol Chem. 2010. PMID: 20356833 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • Wiley

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • GlyGen glycoinformatics resource