Kita Y, Kimura K D, Kobayashi M, Ihara S, Kaibuchi K, Kuroda S, Ui M, Iba H, Konishi H, Kikkawa U, Nagata S, Fukui Y
Department of Biological Chemistry, Faculty of Agricultural and Life Science, University of Tokyo, Tokyo, Japan.
J Cell Sci. 1998 Apr;111 ( Pt 7):907-15. doi: 10.1242/jcs.111.7.907.
We have previously shown that sustained phosphatidylinositol (PI)-3 kinase activity is necessary for neurite outgrowth of PC12 cells induced by nerve growth factor (NGF). Microinjection of a constitutively active mutant of PI-3 kinase induced process formation suggesting that PI-3 kinase is indeed involved in the neurite outgrowth. However, the processes appeared to be incomplete neurites as they had very poor organization of F-actin and GAP43 antigen. The microtubule network was enhanced in the process-bearing cells and process formation was inhibited by colchicine suggesting that microtubules play an important role in process formation downstream of PI-3 kinase. These cell responses were inhibited by dominant-negative mutants of Rac and Sek1/SAPK but not by a dominant-negative mutant Ras and PD98059, a MAP kinase kinase (MEK) inhibitor, suggesting that not the Ras-MAP kinase pathway but the Rac-Jun N-terminal kinase (JNK) pathway is involved in process formation.
我们之前已经表明，持续的磷脂酰肌醇（PI）-3激酶活性对于神经生长因子（NGF）诱导的PC12细胞神经突生长是必需的。显微注射PI-3激酶的组成型活性突变体可诱导突起形成，这表明PI-3激酶确实参与了神经突生长。然而，这些突起似乎是不完全的神经突，因为它们的F-肌动蛋白和GAP43抗原的组织非常差。在有突起的细胞中微管网络增强，并且秋水仙碱可抑制突起形成，这表明微管在PI-3激酶下游的突起形成中起重要作用。这些细胞反应被Rac和Sek1/SAPK的显性负性突变体抑制，但不被显性负性突变体Ras和MAP激酶激酶（MEK）抑制剂PD98059抑制，这表明参与突起形成的不是Ras-MAP激酶途径，而是Rac-Jun N末端激酶（JNK）途径。
