PHOSPHATIDYLINOSITOL 3-KINASE REGULATES PROLIFERATION OF RAW 264.7 MACROPHAGES

Phosphatidylinositol 3-kinase (PI3-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, PI3-kinase inhibitor, decreases the prolifer...

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Veröffentlicht in:Immunopharmacology and immunotoxicology 2001-01, Vol.23 (3), p.355-365
Hauptverfasser: Kim, Hyung-Min, Yim, Hee-Gyun, Yoon, Hyang-Suk, Park, Seung-Taeck, Jeung, Jae-Yeal, Lee, Ki-Nam, Baek, Seung-Hwa, Song, Yung-Sun, Oh, Gyung-Jae, Kim, Nam-Song, An, Nyeon-Hyoung
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container_issue 3
container_start_page 355
container_title Immunopharmacology and immunotoxicology
container_volume 23
creator Kim, Hyung-Min
Yim, Hee-Gyun
Yoon, Hyang-Suk
Park, Seung-Taeck
Jeung, Jae-Yeal
Lee, Ki-Nam
Baek, Seung-Hwa
Song, Yung-Sun
Oh, Gyung-Jae
Kim, Nam-Song
An, Nyeon-Hyoung
description Phosphatidylinositol 3-kinase (PI3-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, PI3-kinase inhibitor, decreases the proliferation of RAW 264.7 macrophages and that another structurally unrelated inhibitor of PI3-kinase, LY294002, also inhibits the proliferation. These results indicate a possible involvement of PI3-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 PI3-kinase plays an important role in growth regulation of RAW 264.7 macrophages and that protein kinase C is a down stream effector of PI3-kinase.
doi_str_mv 10.1081/IPH-100107336
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Here we demonstrate that wortmannin, PI3-kinase inhibitor, decreases the proliferation of RAW 264.7 macrophages and that another structurally unrelated inhibitor of PI3-kinase, LY294002, also inhibits the proliferation. These results indicate a possible involvement of PI3-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 PI3-kinase plays an important role in growth regulation of RAW 264.7 macrophages and that protein kinase C is a down stream effector of PI3-kinase.</abstract><cop>Monticello, NY</cop><pub>Informa UK Ltd</pub><pmid>11694027</pmid><doi>10.1081/IPH-100107336</doi><tpages>11</tpages></addata></record>
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subjects Androstadienes - pharmacology
Animals
Biological and medical sciences
c-fos
c-jun
Cell Cycle - drug effects
Cell cycle, cell proliferation
Cell Division - drug effects
Cell Division - physiology
Cell Line
Cell physiology
Chromones - pharmacology
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Gene Expression - drug effects
Genes, fos - drug effects
Genes, jun - drug effects
Macrophages - cytology
Macrophages - drug effects
Macrophages - enzymology
Mice
Molecular and cellular biology
Morpholines - pharmacology
phorbol 12-myristate 13-acetate
Phosphatidylinositol 3-kinase
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Phosphatidylinositol 3-Kinases - physiology
Protein kinase C
RAW 264.7 macrophages
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tetradecanoylphorbol Acetate - pharmacology
wortmannin
title PHOSPHATIDYLINOSITOL 3-KINASE REGULATES PROLIFERATION OF RAW 264.7 MACROPHAGES
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