Inhibition of ULK2 Autophagic Activity by Its Association with YAP

Sung Hwa Shin, Eun Jeoung Lee, Sunghee Hyun, Dowonkyoung Park, Sang Sun Kang

Abstract


Uncoordinated 51-like kinase 2 (ULK2) is a member of the serine/threonine kinase family that functions an essential role regulating autophagy in mammalian cells. As autophagy is implicated in normal cellular homeostasis and multiple diseases, better mechanisticinsight will drive thedevelopment of novel therapeutic approaches. Here, we present evidence that ULK2 interacts withYAP for its degradation and subcellular localization. A potential PPxY motif (328PPnY331) was identified, which is similar with the consensus PPxY motif in ULK2 S/P domain. TheP329A (PA) mutation in the PY motif of ULK2 abolished the YAP-ULK2 association.At first, we observed that ULK2 physically interacted to YAP in vivo and in vitro, using a pull-down approach. Secondly, ULK2 and YAP co- localized at the apical (or tight junction) membrane as visualized by confocal microscopy. Furthermore, the PA mutant substantially increased during autophagy than that of wild-type ULK2 or the P242A mutant in transient transfection assays. Thus, the association between ULK2 and YAP through the WW domain links autophagy and the Hippo signal transduction pathway.


Full Text:

PDF


DOI: https://doi.org/10.5296/jbls.v8i1.10214

Refbacks

  • There are currently no refbacks.


Copyright (c) 2016 Sung Hwa Shin, Eun Jeoung Lee, Sunghee Hyun, Dowonkyoung Park, Sang Sun Kang

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Journal of Biology and Life Science  ISSN 2157-6076

Copyright © Macrothink Institute

To make sure that you can receive messages from us, please add the 'macrothink.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.