Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Huang B, Yang CS, Wojton J, Huang NJ, Chen C, Soderblom EJ, Zhang L, Kornbluth S.
???displayArticle.abstract???
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.
Andersen,
A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2.
2011, Pubmed,
Xenbase
Andersen,
A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2.
2011,
Pubmed
,
Xenbase Bonzon,
Caspase-2-induced apoptosis requires bid cleavage: a physiological role for bid in heat shock-induced death.
2006,
Pubmed Cheung,
Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: a role for the IAPs.
2006,
Pubmed Colbran,
Regulatory domain of calcium/calmodulin-dependent protein kinase II. Mechanism of inhibition and regulation by phosphorylation.
1989,
Pubmed Colbran,
Regulatory interactions of the calmodulin-binding, inhibitory, and autophosphorylation domains of Ca2+/calmodulin-dependent protein kinase II.
1988,
Pubmed Guo,
Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria.
2002,
Pubmed Hanson,
Inhibitory autophosphorylation of multifunctional Ca2+/calmodulin-dependent protein kinase analyzed by site-directed mutagenesis.
1992,
Pubmed Hanson,
Dual role of calmodulin in autophosphorylation of multifunctional CaM kinase may underlie decoding of calcium signals.
1994,
Pubmed Healy,
CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: identification, characterization, and homology to the B subunit of mammalian type 2A protein phosphatase.
1991,
Pubmed Ho,
A tumor suppressor function for caspase-2.
2009,
Pubmed Kolb,
Identification of domains essential for the assembly of calcium/calmodulin-dependent protein kinase II holoenzymes.
1998,
Pubmed Kolodziej,
Three-dimensional reconstructions of calcium/calmodulin-dependent (CaM) kinase IIalpha and truncated CaM kinase IIalpha reveal a unique organization for its structural core and functional domains.
2000,
Pubmed Lassus,
Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization.
2002,
Pubmed Marganski,
Targeting of a novel Ca+2/calmodulin-dependent protein kinase II is essential for extracellular signal-regulated kinase-mediated signaling in differentiated smooth muscle cells.
2005,
Pubmed Margolis,
Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.
2006,
Pubmed
,
Xenbase McCoy,
Metabolic activation of CaMKII by coenzyme A.
2013,
Pubmed
,
Xenbase McCoy,
Metabolic regulation of CaMKII protein and caspases in Xenopus laevis egg extracts.
2013,
Pubmed
,
Xenbase Meyer,
Calmodulin trapping by calcium-calmodulin-dependent protein kinase.
1992,
Pubmed Nutt,
Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2.
2009,
Pubmed
,
Xenbase Nutt,
Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2.
2005,
Pubmed
,
Xenbase Parsons,
Genetic deletion of caspase-2 accelerates MMTV/c-neu-driven mammary carcinogenesis in mice.
2013,
Pubmed Patton,
Activation of type II calcium/calmodulin-dependent protein kinase by Ca2+/calmodulin is inhibited by autophosphorylation of threonine within the calmodulin-binding domain.
1990,
Pubmed Robertson,
Caspase-2 acts upstream of mitochondria to promote cytochrome c release during etoposide-induced apoptosis.
2002,
Pubmed Rokolya,
Inhibition of CaM kinase II activation and force maintenance by KN-93 in arterial smooth muscle.
2000,
Pubmed Shen,
In vivo and in vitro characterization of the sequence requirement for oligomer formation of Ca2+/calmodulin-dependent protein kinase IIalpha.
1998,
Pubmed Shields,
Identification of protein phosphatase 1 in synaptic junctions: dephosphorylation of endogenous calmodulin-dependent kinase II and synapse-enriched phosphoproteins.
1985,
Pubmed Silva,
Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice.
1992,
Pubmed Smythe,
Systems for the study of nuclear assembly, DNA replication, and nuclear breakdown in Xenopus laevis egg extracts.
1991,
Pubmed
,
Xenbase Sun,
Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity.
1994,
Pubmed Tu,
In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis.
2006,
Pubmed Waxham,
Calcium/calmodulin-dependent protein kinase II regulates hippocampal synaptic transmission.
1993,
Pubmed
