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mTOR independent alteration in ULK1 Ser758 phosphorylation following chronic LRRK2 kinase inhibition

Manzoni, C; Mamais, A; Dihanich, S; Soutar, MPM; Plun-Favreau, H; Bandopadhyay, R; Abeti, R; ... Lewis, PA; + view all (2018) mTOR independent alteration in ULK1 Ser758 phosphorylation following chronic LRRK2 kinase inhibition. Bioscience Reports , 38 (2) , Article BSR20171669. 10.1042/BSR20171669. Green open access

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Abstract

Unc-51 Like Kinase 1 (ULK1) is a critical regulator of the biogenesis of autophagosomes, the central component of the catabolic macroautophagy pathway. Regulation of ULK1 activity is dependent upon several phosphorylation events acting to repress or activate the enzymatic function of this protein. Phosphorylation of Ser758 ULK1 has been linked to repression of autophagosome biogenesis and was thought to be exclusively dependent upon mTOR complex 1 kinase activity. In this study, a novel regulation of Ser758 ULK1 phosphorylation is reported following prolonged inhibition of the Parkinson's disease linked protein Leucine Rich Repeat Kinase 2 (LRRK2). Here, modulation of Ser758 ULK1 phosphorylation following LRRK2 inhibition is decoupled from the repression of autophagosome biogenesis and independent of mTOR complex 1 activity.

Type: Article
Title: mTOR independent alteration in ULK1 Ser758 phosphorylation following chronic LRRK2 kinase inhibition
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1042/BSR20171669
Publisher version: http://doi.org/10.1042/BSR20171669
Language: English
Additional information: Copyright © 2018 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
Keywords: Leucin Rich Repeat Kinase 2 (LRRK2), Parkinson disease, Unc-51 Like Kinase 1 (ULK1), autophagy, cancer, mammalian Target Of Rapamycin (mTOR)
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: http://discovery.ucl.ac.uk/id/eprint/10045902
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