title: Phosphorylation of nucleoporins: signal transduction-mediated regulation of their interaction with nuclear transport receptors.
abstract: The nuclear pore complex (NPC) is composed of ∼30 unique proteins, collectively referred to as nucleoporins or Nups. While metazoan Nups are known to be phosphorylated during mitosis to cause disassembly of the NPC, what is less clear is whether Nups are phosphorylated and regulated by extracellular stimuli in interphase cells. Our multi-step phosphoproteomic approach revealed a number of physiologically relevant extracellular signal-regulated kinase (ERK) targets, including Nups containing FG repeats (FG Nups) that provide binding sites for nuclear transport receptors (NTRs) during the NPC passage. The phosphorylation of FG Nups by ERK does not affect the overall architecture of the NPC but directly inhibits their interactions with NTRs and regulates the permeability barrier properties of the NPC. Such regulation at the levels of transport machinery is expected to have a broad impact on cellular physiology through the spatiotemporal control of signaling events. Until recently, many studies have focused on cellular signaling-mediated phosphorylation of individual cargo proteins, such as transcription factors. An understanding of the effects of signaling pathways on nucleocytoplasmic transport machinery is only beginning to emerge.
authors.affiliation: Division of Disease Proteomics; Institute for Enzyme Research; The University of Tokushima; Tokushima, Japan. kosako@ier.tokushima-u.ac.jp
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Kosako
authors.forename: Naoko
authors.initials: N
authors.lastname: Imamoto
mesh_terms: D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: D028861:Nuclear Pore Complex Proteins; D028961:beta Karyopherins; D048049:Extracellular Signal-Regulated MAP Kinases