The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2


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Athanasopoulos P. S., Heumann R., Kortholt A.

BIOLOGICAL CHEMISTRY, cilt.399, sa.7, ss.643-647, 2018 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 399 Sayı: 7
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1515/hsz-2017-0332
  • Dergi Adı: BIOLOGICAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.643-647
  • Anahtar Kelimeler: GTPase, kinase, neuronal degeneration, Parkinson's disease, phosphatases, DISEASE-ASSOCIATED MUTATIONS, SYNAPTIC VESICLE TRAFFICKING, PARKINSONS-DISEASE, KINASE-ACTIVITY, GTP-BINDING, PHOSPHORYLATION, PENETRANCE, PHENOTYPE, DISRUPTS
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Süleyman Demirel Üniversitesi Adresli: Hayır

Özet

Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson's Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases.