title: Localization and retention of p90 ribosomal S6 kinase 1 in the nucleus: implications for its function.
abstract: Ribosomal S6 kinase 1 (RSK1) belongs to a family of proteins with two kinase domains. Following activation in the cytoplasm by extracellular signal-regulated kinases (ERK1/2), it mediates the cell-proliferative, cell-growth, and survival-promoting actions of a number of growth factors and other agonists. These diverse biological actions of RSK1 involve regulation of both cytoplasmic and nuclear events. However, the mechanisms that permit nuclear accumulation of RSK1 remain unknown. Here, we show that phosphorylation of RSK1 on S221 is important for its dissociation from the type Iα regulatory subunit of protein kinase A (PKA) in the cytoplasm and that RSK1 contains a bipartite nuclear localization sequence that is necessary for its nuclear entry. Once inside, the active RSK1 is retained in the nucleus via its interactions with PKA catalytic subunit and AKAP95. Mutations of RSK1 that do not affect its activity but disrupt its entry into the nucleus or expression of AKAP95 forms that do not enter the nucleus inhibit the ability of active RSK1 to stimulate DNA synthesis. Our findings identify novel mechanisms by which active RSK1 accumulates in the nucleus and also provide new insights into how AKAP95 orchestrates cell cycle progression.
authors: Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors: Xianlong
authors: X
authors: Gao
authors: Deepti
authors: D
authors: Chaturvedi
authors: Tarun B
authors: TB
authors: Patel
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D054758:A Kinase Anchor Proteins; C086194:Akap8 protein, rat; D009687:Nuclear Proteins; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512963:Rps6ka1 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases