Microinjection of activated phosphatidylinositol-3 kinase induces process outgrowth in rat PC12 cells through the Rac-JNK signal transduction pathway

Yoshihiro Kita, Koutarou D. Klmura, Michimoto Kobayashi, Sayoko Lhara, Kozo Kaibuchi, Shinya Kuroda, Motoyasu Ul, Hideo Iba, Hiroaki Konishi, Ushio Kikkawa, Satoshi Nagata, Yasuhisa Fukui

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Abstract

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.

Original languageEnglish
Pages (from-to)907-915
Number of pages9
JournalJournal of cell science
Volume111
Issue number7
Publication statusPublished - 01-01-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Kita, Y., Klmura, K. D., Kobayashi, M., Lhara, S., Kaibuchi, K., Kuroda, S., Ul, M., Iba, H., Konishi, H., Kikkawa, U., Nagata, S., & Fukui, Y. (1998). Microinjection of activated phosphatidylinositol-3 kinase induces process outgrowth in rat PC12 cells through the Rac-JNK signal transduction pathway. Journal of cell science, 111(7), 907-915.