Bak apoptotic function is not directly regulated by phosphorylation
- Author(s)
- Tran, VH; Bartolo, R; Westphal, D; Alsop, A; Dewson, G; Kluck, RM;
- Journal Title
- CELL DEATH & DISEASE
- Publication Type
- Journal Article
- Abstract
- During apoptosis, Bak and Bax permeabilize the mitochondrial outer membrane by undergoing major conformational change and oligomerization. This activation process in Bak is reported to require dephosphorylation of tyrosine-108 close to an activation trigger site. To investigate how dephosphorylation of Bak contributes to its activation and conformational change, one-dimensional isoelectric focusing (1D-IEF) and mutagenesis was used to monitor Bak phosphorylation. On 1D-IEF, Bak extracted from a range of cell types migrated as a single band near the predicted isoelectric point of 5.6 both before and after phosphatase treatment, indicating that Bak is not significantly phosphorylated at any residue. In contrast, three engineered 'phosphotagged' Bak variants showed a second band at lower pI, indicating phosphorylation. Apoptosis induced by several stimuli failed to alter Bak pI, indicating little change in phosphorylation status. In addition, alanine substitution of tyrosine-108 and other putative phosphorylation sites failed to enhance Bak activation or pro-apoptotic function. In summary, Bak is not significantly phosphorylated at any residue, and Bak activation during apoptosis does not require dephosphorylation. Cell Death and Disease (2013) 4, e452; doi:10.1038/cddis.2012.191; published online 10 January 2013
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- BCL-2 PROTEIN FAMILY; TYROSINE DEPHOSPHORYLATION; CONFORMATIONAL-CHANGES; CELL-SURVIVAL; BH3 DOMAIN; ACTIVATION; BINDING; OLIGOMERIZATION; MITOCHONDRIA; INHIBITION
- Research Division(s)
- Cell Signalling And Cell Death; Molecular Genetics Of Cancer
- Publisher's Version
- https://doi.org/10.1038/cddis.2012.191
- Open Access at Publisher's Site
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563979/- Terms of Use/Rights Notice
- Copyright © 2013 Macmillan Publishers Limited This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
Creation Date: 2013-01-01 12:00:00