PuSH - Publikationsserver des Helmholtz Zentrums München: Phosphopeptide analysis reveals two discrete clusters of phosphorylation in the N-terminus and the Roc domain of the Parkinson-disease associated protein kinase LRRK2.

Navigation

Startseite

English

Recherche

Erweiterte Suche

Durchblättern nach ...

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Erscheinungsjahr

Publikationen im Überblick

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Gloeckner, C.J. ; Boldt, K. ; von Zweydorf, F. ; Helm, S. ; Wiesent, L. ; Sarioglu, H. ; Ueffing, M.

Phosphopeptide analysis reveals two discrete clusters of phosphorylation in the N-terminus and the Roc domain of the Parkinson-disease associated protein kinase LRRK2.

J. Proteome Res. 9, 1738-1745 (2010)

DOI

PMC

Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

Abstract
Metriken
Zusatzinfos

Mutations in leucine-rich repeat kinase 2 (LRRK2) that increase its kinase activity associate with familial forms of Parkinson disease (PD). As phosphorylation determines the functional state of most protein kinases, we systematically mapped LRRK2 phosphorylation sites by mass spectrometry. Our analysis revealed a high degree of constitutive phosphorylation in a narrow serine-rich region preceding the LRR-domain. Allowing de novo autophosphorylation of purified LRRK2 in an in vitro autokinase assay prior to mass spectrometric analysis, we discovered multiple sites of autophosphorylation. Solely serine and threonine residues were found phosphorylated suggesting LRRK2 as a true serine threonine kinase. Autophosphorylation mainly targets the ROC GTPase domain and its clustering around the GTP binding pocket of ROC suggests cross-regulatory activity between kinase and Roc domain. In conclusion, the phosphoprotein LRRK2 functions as an autocatalytically active serine threonine kinase. Clustering of phosphosites within two discrete domains suggest that phosphorylation may regulate its biological functions in a yet unknown fashion.

Altmetric

Weitere Metriken?

[➜Einloggen]