BioProject

Reversible phosphorylation is a critical step in the control of cellular signaling events. More...

Reversible phosphorylation is a critical step in the control of cellular signaling events. The protein phosphatase 1 (PP1) regulates neuronal proteins by mediating their de-phosphorylation. PP1 selectivity and subcellular localization is conferred via association with a panel of interacting proteins. We have extensively characterized the association of PP1 with inhibitor-1, an interacting protein widely expressed in brain and heart. Inhibitor-1 deletion results in a persistently active PP1 phosphatase in vitro. Inhibitor-1 overexpression results in increased transformation of cultured cells and enhances the rate of learning and memory in mouse models through largely unknown mechanisms. Significantly, inhibitor-1 activation is cAMP-sensitive. The genes regulated by inhibitor-1/PP1 signals have not been characterized. Identification of these genes is expected to provide key insights into the role of inhibitor-1/PP1 escape from cellular homeostasis and regulation of neuronal learning and memory. We will determine gene expression patterns in hippocampus of wild-type and inhibitor-1 knock-out mice. The results of these studies of constitutive expression will be used as a baseline for future studies aimed to determine the role cAMP-mediated gene expression in I-1 knock-out mice. We hypothesize that the genes regulated by the inhibitor-1/PP1 holoenzyme are critical to cellular growth commitment including resistance to growth arrest and neuronal learning and memory We will examine the role of inhibitor-1 in regulating hippocampal gene expression using total RNA isolated from whole hippocampi of inhibitor-1 knockout (I-1-/-) animals and parental C57Bl6 controls under non-stimulated conditions. Animals will be sacrificed by a standard protocol. Hippocampal tissue will be rapidly dissected from several animals, flash frozen within 1 minute of extraction, pooled, and total RNA will be processed immediately using TriZol. Keywords: dose response Less...