Premium
Protein kinase G phosphorylates the Alzheimer's disease‐associated tau protein at distinct Ser/Thr sites
Author(s) -
Montalto Giulia,
Caudano Francesca,
Sturla Laura,
Bruzzone Santina,
Salis Annalisa,
Damonte Gianluca,
Prickaerts Jos,
Fedele Ernesto,
Ricciarelli Roberta
Publication year - 2021
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1705
Subject(s) - phosphorylation , tau protein , neuroprotection , microbiology and biotechnology , in vivo , kinase , protein kinase a , alzheimer's disease , chemistry , protein aggregation , cyclin dependent kinase 5 , neuroscience , biology , disease , medicine , cyclin dependent kinase 2 , genetics
Intraneuronal accumulation of hyperphosphorylated tau is a pathological hallmark of several neurodegenerative disorders, including Alzheimer's disease. Phosphorylation plays a crucial role in modulating the tau‐microtubule interaction and the ability of the protein to aggregate, but despite efforts during the past decades, the real identity of the kynases involved in vivo remains uncertain. Here, for the first time, we demonstrate that the cGMP‐dependent protein kinase G (PKG) phosphorylates tau in both in vitro and in vivo models. More intriguingly, we provide evidence that PKG phosphorylates tau at Ser214 but not at Ser202, a condition that could reduce the pathological aggregation of the protein shifting tau from a pro‐aggregant to a neuroprotective anti‐aggregant conformation.