title: FR225659-binding proteins: identification as serine/threonine protein phosphatase PP1 and PP2A using high-performance affinity beads.
abstract: FR225659 was originally isolated as a novel gluconeogenesis inhibitor produced by fungal strain Helicomyces sp. No. 19353. To identify the target protein of FR225659, we synthesized high-performance affinity latex beads that immobilized FR225659 derivative FR253761 or FR259383. Using these beads, we identified FR225659 binding proteins as serine/threonine protein phosphatase type1 (PP1) and type2A (PP2A) from rat hepatocyte crude extract. FR225659 and its synthetic derivatives were strongly inhibited the enzyme activities of purified catalytic subunits of PP1 and PP2A in vitro.
authors.affiliation: Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. hidetaka_hatori@po.fujisawa.co.jp
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hatori
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Zenkoh
authors.forename: Motoo
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohtsu
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Shigematsu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Setoi
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000302:isolation & purification* / Q000378:metabolism; D005943:Gluconeogenesis; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000302:isolation & purification* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: C478488:(4-hydroxy-3-(2-(2-propenyl)-4-quinoline)benzoyl)-(3-chloro-4-hydroxyarginyl)-(3-hydroxy-3-methylprolyl)-dehydrovaline; D002352:Carrier Proteins; D009842:Oligopeptides; D010749:Phosphoprotein Phosphatases