Microinjection of activated phosphatidylinositol-3 kinase induces process outgrowth in rat PC12 cells through the Rac-JNK signal transduction pathway.
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.
Kita
Y
Y
Department of Biological Chemistry, Faculty of Agricultural and Life Science, University of Tokyo, Tokyo, Japan.
Kimura
K D
KD
Kobayashi
M
M
Ihara
S
S
Kaibuchi
K
K
Kuroda
S
S
Ui
M
M
Iba
H
H
Konishi
H
H
Kikkawa
U
U
Nagata
S
S
Fukui
Y
Y
D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D005822:Genetic Vectors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008845:Microinjections; D020928:Mitogen-Activated Protein Kinases; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells / Q000166:cytology* / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D020744:rac GTP-Binding Proteins
D019869:Phosphatidylinositol 3-Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins