Phosphatidylinositol 3-kinase regulates proliferation of RAW 264.7 macrophages.
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.
Kim
H M
HM
College of Pharmacy, Korea Institute of Oriental Pharmacy, Wonkwang University School of Medicine, Iksan, Chonbuk, Republic of Korea. hmkim@wonkwang.ac.kr
Yim
H G
HG
Yoon
H S
HS
Park
S T
ST
Jeung
J Y
JY
Lee
K N
KN
Baek
S H
SH
Song
Y S
YS
Oh
G J
GJ
Kim
N S
NS
An
N H
NH
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
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