期刊
CELL DEATH & DISEASE
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2012.191
关键词
apoptosis; Bak phosphorylation; Bak activation; Bcl-2 proteins; isoelectric focusing; tyrosine phosphorylation
类别
资金
- National Health and Medical Research Council of Australia [575559, 1016701, 637335]
- Association for International Cancer Research [10-230]
- Victorian State Government Operational Intrastructure Support
- Australian Government NHMRC IRIISS
- Worldwide Cancer Research [10-0230] Funding Source: researchfish
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
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