title: Phosphatidylinositol 3-kinase regulates proliferation of RAW 264.7 macrophages.
abstract: Phosphatidylinositol 3-kinase (P13-kinase) is an enzyme that acts as a direct biochemical link between a novel phosphatidylinositol pathway and a number of proteins containing intrinsic or associated kinase activities. Here we demonstrate that wortmannin, P13-kinase inhibitor, decreases the proliferation of RAW 264.7 macrophages and that another structurally unrelated inhibitor of P13-kinase, LY294002. also inhibits the proliferation. These results indicate a possible involvement of P13-kinase in RAW 264.7 macrophages growth regulation. Wortmannin stimulation of RAW 264.7 macrophages is followed by sustained expression of the mRNA of c-fos and a transient expression of the mRNA of c-jun. We also show that the wortmannin and LY294002 induce a cell cycle arrest in asynchronously growing cells leading to an inhibition of cell proliferation after 12 h of treatment. In addition, wortmannin or LY294002 inhibited the phorbol 12-myristate 13-acetate-induced macrophages proliferation potently. These results suggest that P13-kinase plays an important role in growth regulation of RAW 264.7 macrophages and that protein kinase C is a down stream effector of P13-kinase.
authors.affiliation: College of Pharmacy, Korea Institute of Oriental Pharmacy, Wonkwang University School of Medicine, Iksan, Chonbuk, Republic of Korea. hmkim@wonkwang.ac.kr
authors.forename: H M
authors.initials: HM
authors.lastname: Kim
authors.forename: H G
authors.initials: HG
authors.lastname: Yim
authors.forename: H S
authors.initials: HS
authors.lastname: Yoon
authors.forename: S T
authors.initials: ST
authors.lastname: Park
authors.forename: J Y
authors.initials: JY
authors.lastname: Jeung
authors.forename: K N
authors.initials: KN
authors.lastname: Lee
authors.forename: S H
authors.initials: SH
authors.lastname: Baek
authors.forename: Y S
authors.initials: YS
authors.lastname: Song
authors.forename: G J
authors.initials: GJ
authors.lastname: Oh
authors.forename: N S
authors.initials: NS
authors.lastname: Kim
authors.forename: N H
authors.initials: NH
authors.lastname: An
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one