title: RKIP structure drives its function: a three-state model for regulation of RKIP.
abstract: Raf kinase inhibitory protein (RKIP) is a highly conserved regulator of many signaling networks whose loss or inactivation can lead to a variety of disease states. The multifaceted roles played by RKIP are enabled by an allosteric structure that is controlled through phosphorylation of RKIP and dynamics in the RKIP pocket loop. Perhaps the most striking feature of RKIP is that it can assume multiple functional states. Specifically, phosphorylation redirects RKIP from a state that binds and inhibits Raf-1 to a state that binds and inhibits GRK2. Recent evidence suggests the presence of a third functional state that facilitates RKIP phosphorylation. Here, we present a three-state model to explain the RKIP functional switch and discuss the role of the pocket loop in regulating RKIP activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois.
authors.forename: John J
authors.initials: JJ
authors.lastname: Skinner
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Gordon Center for Integrative Sciences, Chicago, Illinois.
authors.forename: Marsha Rich
authors.initials: MR
authors.lastname: Rosner
mesh_terms: D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D049488:Phosphatidylethanolamine Binding Protein / Q000737:chemistry* / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D010743:Phospholipids; D019908:Proto-Oncogene Proteins c-raf