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XB-ART-46660
J Biol Chem March 29, 2013; 288 (13): 8838-48.

Metabolic regulation of CaMKII protein and caspases in Xenopus laevis egg extracts.

McCoy F , Darbandi R , Chen SI , Eckard L , Dodd K , Jones K , Baucum AJ , Gibbons JA , Lin SH , Colbran RJ , Nutt LK .


Abstract
The metabolism of the Xenopus laevis egg provides a cell survival signal. We found previously that increased carbon flux from glucose-6-phosphate (G6P) through the pentose phosphate pathway in egg extracts maintains NADPH levels and calcium/calmodulin regulated protein kinase II (CaMKII) activity to phosphorylate caspase 2 and suppress cell death pathways. Here we show that the addition of G6P to oocyte extracts inhibits the dephosphorylation/inactivation of CaMKII bound to caspase 2 by protein phosphatase 1. Thus, G6P sustains the phosphorylation of caspase 2 by CaMKII at Ser-135, preventing the induction of caspase 2-mediated apoptotic pathways. These findings expand our understanding of oocyte biology and clarify mechanisms underlying the metabolic regulation of CaMKII and apoptosis. Furthermore, these findings suggest novel approaches to disrupt the suppressive effects of the abnormal metabolism on cell death pathways.

PubMed ID: 23400775
PMC ID: PMC3610959
Article link: J Biol Chem
Grant support: [+]
Genes referenced: acta1 actl6a camk2a camk2b camk2g casp2 gapdh npy4r ppp1ca ppp1cb ppp1cc ppp1r9a ptpa rpsa
Antibodies: Acta1 Ab2 Calm1 Ab1 Camk2 Ab1 Camk2a Ab1 Camk2a/b Ab1 FLAG Ab3 Gapdh Ab2 Gstk1 Ab2 Ppp1ca Ab1 Ppp1cb Ab1 Ppp1cc Ab1


Article Images: [+] show captions
References [+] :
Baucum, Age-dependent targeting of protein phosphatase 1 to Ca2+/calmodulin-dependent protein kinase II by spinophilin in mouse striatum. 2012, Pubmed


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