title: Regulation of the phosphatase PP2B by protein-protein interactions.
abstract: Protein dephosphorylation is important for regulating cellular signaling in a variety of contexts. Protein phosphatase-2B (PP2B), or calcineurin, is a widely expressed serine/threonine phosphatase that acts on a large cross section of potential protein substrates when activated by increased levels of intracellular calcium in concert with calmodulin. PxIxIT and LxVP targeting motifs are important for maintaining specificity in response to elevated calcium. In the present study, we describe the mechanism of PP2B activation, discuss its targeting by conserved binding motifs and review recent advances in the understanding of an A-kinase anchoring protein 79/PP2B/protein kinase A complex's role in synaptic long-term depression. Finally, we discuss potential for targeting PP2B anchoring motifs for therapeutic benefit.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.|Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Nygren
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.|Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Scott
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D036881:Long-Term Synaptic Depression; D008954:Models, Biological; D011485:Protein Binding
chemical_list: D054758:A Kinase Anchor Proteins; C487775:AKAP5 protein, human; D002147:Calmodulin; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin; D002118:Calcium
keywords: AKAP79; PP2B; anchoring protein; calcineurin; phosphatase; synaptic plasticity