Metabolic control of Ca2+/calmodulin-dependent protein kinase II (CaMKII)-mediated caspase-2 suppression by the B55β/protein phosphatase 2A (PP2A).
Published
Journal Article
High levels of metabolic activity confer resistance to apoptosis. Caspase-2, an apoptotic initiator, can be suppressed by high levels of nutrient flux through the pentose phosphate pathway. This metabolic control is exerted via inhibitory phosphorylation of the caspase-2 prodomain by activated Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). We show here that this activation of CaMKII depends, in part, on dephosphorylation of CaMKII at novel sites (Thr(393)/Ser(395)) and that this is mediated by metabolic activation of protein phosphatase 2A in complex with the B55β targeting subunit. This represents a novel locus of CaMKII control and also provides a mechanism contributing to metabolic control of apoptosis. These findings may have implications for metabolic control of the many CaMKII-controlled and protein phosphatase 2A-regulated physiological processes, because both enzymes appear to be responsive to alterations in glucose metabolized via the pentose phosphate pathway.
Full Text
Duke Authors
Cited Authors
- Huang, B; Yang, C-S; Wojton, J; Huang, N-J; Chen, C; Soderblom, EJ; Zhang, L; Kornbluth, S
Published Date
- December 26, 2014
Published In
Volume / Issue
- 289 / 52
Start / End Page
- 35882 - 35890
PubMed ID
- 25378403
Pubmed Central ID
- 25378403
Electronic International Standard Serial Number (EISSN)
- 1083-351X
Digital Object Identifier (DOI)
- 10.1074/jbc.M114.585844
Language
- eng
Conference Location
- United States