Metabolic control of Ca2+/Calmodulin-dependent protein kinase II (CaMKII)-mediated Caspase-2 suppression by the B55{beta}/protein phosphatase 2A (PP2A) [Signal Transduction]

November 4th, 2014 by Huang, B., Yang, C.-S., Wojton, J., Huang, N.-J., Chen, C., Soderblom, E. J., Zhang, L., Kornbluth, S.

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 (PPP). This metabolic control is exerted via inhibitory phosphorylation of the caspase-2 pro-domain by activated Ca2+/Calmodulin-dependent protein kinase II (CaMKII). We show here that this activation of CaMKII depends, in part, on dephosphorylation of CaMKII at novel sites (T393/S395) and that this is mediated by metabolic activation of protein phosphatase 2A (PP2A) 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 PP2A-regulated physiological processes, as both enzymes appear to be responsive to alterations in glucose metabolized via the PPP.
  • Posted in Journal of Biological Chemistry, Publications
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