Activation mechanism of c-Jun amino-terminal kinase in the course of neural differentiation of P19 embryonic carcinoma cells

被引:17
作者
Akiyama, S
Yonezawa, T
Kudo, TA
Li, MG
Wang, H
Ito, M
Yoshioka, K
Ninomiya-Tsuji, J
Matsumoto, K
Kanamaru, R
Tamura, S
Kobayashi, T
机构
[1] Tohoku Univ, Inst Dev Aging & Canc, Dept Biochem, Aoba Ku, Sendai, Miyagi 9808575, Japan
[2] Tohoku Univ, Inst Dev Aging & Canc, Dept Clin Oncol, Aoba Ku, Sendai, Miyagi 9808575, Japan
[3] Kitasato Univ, Sch Sci, Dept Biosci, Kanagawa 2288555, Japan
[4] Kanazawa Univ, Canc Res Inst, Div Cell Cycle Regulat, Kanazawa, Ishikawa 9200934, Japan
[5] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA
[6] Nagoya Univ, Grad Sch Sci, Dept Mol Biol, Chikusa Ku, Nagoya, Aichi 4648602, Japan
关键词
D O I
10.1074/jbc.M406610200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
P19 embryonic carcinoma cells, a model system for studying early development and differentiation, can differentiate into neurons and primitive endoderm-like cells depending on the culture conditions. We have previously reported that the activation of c-Jun amino-terminal kinase (JNK) is required for the retinoic acid-induced neural differentiation of P19 cells. However, the signaling pathway(s) responsible for the activation of JNK has not been known. In this study, we demonstrated that activities of MAPK kinase 4 (MKK4) and TAK1, one of the upstream kinases of MKK4, were enhanced in the neurally differentiating cells. Inhibition of the neural differentiation by an overexpression of protein phosphatase 2Cepsilon, an inactivator of TAK1, suggested a critical role of the TAK1 signaling pathway during the differentiation. Confocal microscopic analysis indicated that TAK1, phospho-MKK4, and phospho-JNK were colocalized with tubulin in the neurites and localized also in the nuclei of the differentiating cells. In contrast, two TAK1-binding proteins, TAB1 and TAB2, which are involved in the activation of TAK1, were localized in the neurites and the nuclei of the differentiating cells, respectively. These results suggest that two distinct TAK1-MKK4-JNK signaling pathways are independently activated at the different intracellular locations and may participate in the regulation of the neural differentiation of P19 cells.
引用
收藏
页码:36616 / 36620
页数:5
相关论文
共 36 条
  • [21] A novel SAPK/JNK kinase, MKK7, stimulated by TNFα and cellular stresses
    Moriguchi, T
    Toyoshima, F
    Masuyama, N
    Hanafusa, H
    Gotoh, Y
    Nishida, E
    [J]. EMBO JOURNAL, 1997, 16 (23) : 7045 - 7053
  • [22] The kinase TAK1 can activate the NIK-IκB as well as the MAP kinase cascade in the IL-1 signalling pathway
    Ninomiya-Tsuji, J
    Kishimoto, K
    Hiyama, A
    Inoue, J
    Cao, ZD
    Matsumoto, K
    [J]. NATURE, 1999, 398 (6724) : 252 - 256
  • [23] IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of N-FκB
    Qian, YC
    Commane, M
    Ninomiya-Tsuji, J
    Matsumoto, K
    Li, XX
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (45) : 41661 - 41667
  • [24] Reynolds CH, 1997, J NEUROCHEM, V69, P191
  • [25] Robertson E.J., 1987, PRACTICAL APPROACH T, P19
  • [26] Molecular cloning and functional expression of a cDNA encoding a new member of mixed lineage protein kinase from human brain
    Sakuma, H
    Ikeda, A
    Oka, S
    Kozutsumi, Y
    Zanetta, JP
    Kawasaki, T
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (45) : 28622 - 28629
  • [27] SANCHEZ I, 1994, NATURE, V372, P794, DOI 10.1038/372794a0
  • [28] Okadaic acid suppresses neural differentiation-dependent expression of the neurofilament-L gene in P19 embryonal carcinoma cells by post-transcriptional modification
    Sasahara, Y
    Kobayashi, T
    Onodera, H
    Onoda, M
    Ohnishi, M
    Kato, S
    Kusuda, K
    Shima, H
    Nagao, M
    Abe, H
    Yanagawa, Y
    Hiraga, A
    Tamura, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (42) : 25950 - 25957
  • [29] Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway
    Takaesu, G
    Ninomiya-Tsuji, J
    Kishida, S
    Li, XX
    Stark, GR
    Matsumoto, K
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (07) : 2475 - 2484
  • [30] MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6
    Tibbles, LA
    Ing, YL
    Kiefer, F
    Chan, J
    Iscove, N
    Woodgett, JR
    Lassam, NJ
    [J]. EMBO JOURNAL, 1996, 15 (24) : 7026 - 7035