Metabolic control of Ca2+/calmodulin-dependent protein kinase II (CaMKII)-mediated caspase-2 suppression by the B55β/protein phosphatase 2A (PP2A).

Journal Article (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

  • PMC4276857

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M114.585844


  • eng

Conference Location

  • United States