1 research outputs found
Efficient Modification of Alpha-Synuclein Serine 129 by Protein Kinase CK1 Requires Phosphorylation of Tyrosine 125 as a Priming Event
S129-phosphorylated
alpha-synuclein (α-syn) is abundantly
found in Lewy-body inclusions of Parkinson’s disease patients.
Residues neighboring S129 include the α-syn tyrosine phosphorylation
sites Y125, Y133, and Y136. Here, we use time-resolved NMR spectroscopy
to delineate atomic resolution insights into the modification behaviors
of different serine and tyrosine kinases targeting these sites and
show that Y125 phosphorylation constitutes a necessary priming event
for the efficient modification of S129 by CK1, both in reconstituted
kinase reactions and mammalian cell lysates. These results suggest
that α-syn Y125 phosphorylation augments S129 modification under
physiological in vivo conditions