Neurite outgrowth of PC12 cells is suppressed by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase.
The effects of wortmannin (WT), an inhibitor of phosphatidylinositol (PI) 3-kinase, on differentiation of PC12 cells were analyzed. WT inhibited PI 3-kinase activity of PC12 cells at a concentration of 10(-7) M in vivo and in vitro. Transient inhibition of PI 3-kinase activity at the time of nerve growth factor stimulation had no effect on activation of the ras protein or neurite formation by the cells. However, continuous inhibition of PI 3-kinase blocked differentiation at the step just before neurite formation. When WT was applied to cells growing neurites, elongation of the neurites was stopped at that step. These results suggest that PI 3-kinase may be involved in neurite elongation.
Department of Applied Biological Chemistry, University of Tokyo, Japan.
K
K
Kimura
S
S
Hattori
Y
Y
Kabuyama
Y
Y
Shizawa
J
J
Takayanagi
S
S
Nakamura
S
S
Toki
Y
Y
Matsuda
K
K
Onodera
Y
Y
Fukui
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000648:ultrastructure*; D009474:Neurons / Q000166:cytology*; D016716:PC12 Cells / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D009414:Nerve Growth Factors; D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D000077191:Wortmannin