Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 325, Issue 1, Pages 203-214Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.10.021
Keywords
calphoglin; calcineurin; phosphoglucommase; inorganic pyrophospbatase
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Universal protein networks conserved from bacteria to animals dictate the core functions of cells. Inorganic pyrophosphatase (IPP) is an essential enzyme that plays a pivotal role in a broad spectrum of cellular biosynthetic reactions such as amino acid, nucleotide, polysaccharide, and fatty acid biosynthesis. However, the in vivo cellular regulation mechanisms of IPP and another key metabolic enzyme, phosphoglucommase (PGM), remain unknown. This study aimed to examine the universal protein regulatory network by utilizing genome sequences, yeast proteomic data, and phosphoryl-transfer experiments. Here we report a novel human protein, henceforth referred to as calphoglin, which interacts with IPP and activates it. Calphoglin enhances PGM activity through the activated IPP and more directly on its own. Protein structure and assembly, catalytic function, and ubiquitous cellular localization of the calphoglin (-IPP-PGM) complex were conserved among Escherichia coli, yeast, and mammals. In the rat brain, calphoglin mRNA was enriched in the hippocampus and the cerebellum. Further, the linkage of the calphoglin complex to calcium signaling was demonstrated by its interactive co-localization within the calmodulin/calcineurin signaling complex, by Ca2+ -binding and Ca2+-controlled activity of calphoglin-IPP, and by calphoglin-induced enhancement of microsomal Ca2+ uptake. Collectively, these results suggest that the calphoglin complex is a common mechanism utilized in mediating bacterial cell metabolism and Ca2+/ calmodulin/calcineurin-dependent mammalian cell activation. This is the first report of an activator of IPP and PGM, a function novel to proteins. (C) 2004 Elsevier Inc. All rights reserved.
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