sikes-affy-mouse-84486

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.

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