RRC ID 39649
著者 Takeda K, Hatai T, Hamazaki TS, Nishitoh H, Saitoh M, Ichijo H.
タイトル Apoptosis signal-regulating kinase 1 (ASK1) induces neuronal differentiation and survival of PC12 cells.
ジャーナル J Biol Chem
Abstract Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase that activates the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase signaling cascades. We report here that expression of constitutively active ASK1 (ASK1DeltaN) induces neurite outgrowth in the rat pheochromocytoma cell line PC12. We found that p38 and to a lesser extent JNK, but not ERK, were activated by the expression of ASK1DeltaN in PC12 cells. ASK1DeltaN-induced neurite outgrowth was strongly inhibited by treatment with the p38 inhibitor SB203580 but not with the MEK inhibitors, suggesting that activation of p38, rather than of ERK, is required for the neurite-inducing activity of ASK1 in PC12 cells. We also observed that ASK1DeltaN induced expression of several neuron-specific proteins and phosphorylation of neurofilament proteins, confirming that PC12 cells differentiated into mature neuronal cells by ASK1. Moreover, ASK1DeltaN-expressing PC12 cells survived in serum-starved condition. ASK1 thus appears to mediate signals leading to both differentiation and survival of PC12 cells. Together with previous reports indicating that ASK1 functions as a pro-apoptotic signaling intermediate, these results suggest that ASK1 has a broad range of biological activities depending on cell types and/or cellular context.
巻・号 275(13)
ページ 9805-13
公開日 2000-3-31
DOI 10.1074/jbc.275.13.9805
PII S0021-9258(18)30102-9
PMID 10734135
MeSH Animals Arabidopsis Proteins* Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors Calcium-Calmodulin-Dependent Protein Kinases / metabolism Cell Differentiation / physiology* Cell Survival / physiology* Culture Media, Serum-Free Enzyme Activation Enzyme Inhibitors / pharmacology Imidazoles / pharmacology Mitogen-Activated Protein Kinases* Neurites Neurons / cytology* PC12 Cells Plant Proteins / physiology* Pyridines / pharmacology Rats p38 Mitogen-Activated Protein Kinases
IF 4.238
引用数 136
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 PC-12(RCB0009)