TY - JOUR
T1 - Expression of a constitutively active phosphatidylinositol 3-kinase induces process formation in rat PC12 cells
AU - Kobayashi, Michimoto
AU - Nagata, Satoshi
AU - Kita, Yoshihiro
AU - Nakatsu, Noriyuki
AU - Ihara, Sayoko
AU - Kaibuchi, Kozo
AU - Kuroda, Shinya
AU - Ui, Motoyasu
AU - Iba, Hideo
AU - Konishi, Hiroaki
AU - Kikkawa, Ushio
AU - Saitoh, Izumu
AU - Fukui, Yasuhisa
PY - 1997/6/27
Y1 - 1997/6/27
N2 - It has been shown that inhibition of phosphatidylinositol (PI) 3-kinase blocks neurite outgrowth of PC12 cells stimulated with nerve growth factor. To further assess the role of PI 3-kinase, the active form of PI 3-kinase was expressed in PC12 cells by the adenovirus mediated introduction of a site- specific recombinase, Cre. After expression of the active PI 3-kinase, elevation of the levels of PI 3,4-diphosphate and PI 3,4,5-trisphosphate as well as formation of neurite-like processes was observed. The process formation was inhibited by wort-mannin, a selective inhibitor of PI 3- kinase, which suggests that a high activity of PI 3-kinase was responsible for the formation of these processes. The processes lacked accumulation of F- actin and GAP43 at the growth cone, which suggests that the processes were incomplete compared with neurites. Instead, the bundling of microtubules was enhanced, which suggests that organization of the microtubules might be driving the process of elongation in the cells expressing the active PI 3- kinase. Induction of active PI 3-kinase resulted in activation of Jun N- terminal kinase but not of mitogen-activated protein kinase or protein kinase B/Rac protein kinase/Akt. These results suggest that PI 3-kinase is involved in neurite outgrowth in PC12 cells and that activation of Jun N-terminal kinase cascade may be involved in the cell response.
AB - It has been shown that inhibition of phosphatidylinositol (PI) 3-kinase blocks neurite outgrowth of PC12 cells stimulated with nerve growth factor. To further assess the role of PI 3-kinase, the active form of PI 3-kinase was expressed in PC12 cells by the adenovirus mediated introduction of a site- specific recombinase, Cre. After expression of the active PI 3-kinase, elevation of the levels of PI 3,4-diphosphate and PI 3,4,5-trisphosphate as well as formation of neurite-like processes was observed. The process formation was inhibited by wort-mannin, a selective inhibitor of PI 3- kinase, which suggests that a high activity of PI 3-kinase was responsible for the formation of these processes. The processes lacked accumulation of F- actin and GAP43 at the growth cone, which suggests that the processes were incomplete compared with neurites. Instead, the bundling of microtubules was enhanced, which suggests that organization of the microtubules might be driving the process of elongation in the cells expressing the active PI 3- kinase. Induction of active PI 3-kinase resulted in activation of Jun N- terminal kinase but not of mitogen-activated protein kinase or protein kinase B/Rac protein kinase/Akt. These results suggest that PI 3-kinase is involved in neurite outgrowth in PC12 cells and that activation of Jun N-terminal kinase cascade may be involved in the cell response.
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U2 - 10.1074/jbc.272.26.16089
DO - 10.1074/jbc.272.26.16089
M3 - Article
C2 - 9195902
AN - SCOPUS:0030917921
SN - 0021-9258
VL - 272
SP - 16089
EP - 16092
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 26
ER -