Apoptosis-signal regulating kinase-1 is involved in the low potassium-induced activation of p38 mitogen-activated protein kinase and c-Jun in cultured cerebellar granule neurons

Satoru Yamagishi, Masashi Yamada, Hisatsugu Koshimizu, Satomi Takai, Hiroshi Hatanaka, Kohsuke Takeda, Hidenori Ichijo, Koji Shimoke, Toshihiko Ikeuchi

Research output: Contribution to journalArticle

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Abstract

Previously, we reported that p38, which belongs to the mitogen-activated protein kinase (MAPK) superfamily, has an important role in the induction of apoptosis of cultured cerebellar granule neurons. However, the molecular mechanisms upstream of p38 activation remain unclear. Apoptosis signal-regulating kinase-1 (ASK1), a MAPK kinase kinase (MAPKKK) protein, is known to activate both c-Jun N-terminal kinase (JNK) and p38 via MAPK kinase (MKK) 4/7 and MKK3/6, respectively. Here, we examined whether ASK1 is involved in the activation of p38 in the low potassium (LK)-induced apoptosis of cerebellar granule neurons. We found that ASK1 was activated after a change to LK medium. In addition, the expression of ASK1-KM, a dominant-negative form of ASK1, using an adenovirus system was found to inhibit the activation of p38 and c-Jun and to prevent apoptosis. On the other hand, the expression of ASK1-ΔN, a constitutively active form of ASK1, activated p38 and c-Jun, but not JNK, another possible downstream target of ASK1. Furthermore, we examined the relationship between phosphatidylinositol 3-kinase (PI3-K) and ASK1. The addition of LY294002, a specific inhibitor of PI3-K, enhanced the ASK1 activity. These results indicate that ASK1 works downstream of PI3-K to regulate the p38-c-Jun pathway and apoptosis in cultured cerebellar granule neurons.

Original languageEnglish
Pages (from-to)719-724
Number of pages6
JournalJournal of Biochemistry
Volume133
Issue number6
DOIs
Publication statusPublished - 01-06-2003

Fingerprint

MAP Kinase Kinase Kinase 5
p38 Mitogen-Activated Protein Kinases
Neurons
Potassium
Chemical activation
Phosphatidylinositol 3-Kinase
Apoptosis
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase 7
MAP Kinase Kinase 4
MAP Kinase Kinase Kinases
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Mitogen-Activated Protein Kinases
Adenoviridae

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Yamagishi, Satoru ; Yamada, Masashi ; Koshimizu, Hisatsugu ; Takai, Satomi ; Hatanaka, Hiroshi ; Takeda, Kohsuke ; Ichijo, Hidenori ; Shimoke, Koji ; Ikeuchi, Toshihiko. / Apoptosis-signal regulating kinase-1 is involved in the low potassium-induced activation of p38 mitogen-activated protein kinase and c-Jun in cultured cerebellar granule neurons. In: Journal of Biochemistry. 2003 ; Vol. 133, No. 6. pp. 719-724.
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abstract = "Previously, we reported that p38, which belongs to the mitogen-activated protein kinase (MAPK) superfamily, has an important role in the induction of apoptosis of cultured cerebellar granule neurons. However, the molecular mechanisms upstream of p38 activation remain unclear. Apoptosis signal-regulating kinase-1 (ASK1), a MAPK kinase kinase (MAPKKK) protein, is known to activate both c-Jun N-terminal kinase (JNK) and p38 via MAPK kinase (MKK) 4/7 and MKK3/6, respectively. Here, we examined whether ASK1 is involved in the activation of p38 in the low potassium (LK)-induced apoptosis of cerebellar granule neurons. We found that ASK1 was activated after a change to LK medium. In addition, the expression of ASK1-KM, a dominant-negative form of ASK1, using an adenovirus system was found to inhibit the activation of p38 and c-Jun and to prevent apoptosis. On the other hand, the expression of ASK1-ΔN, a constitutively active form of ASK1, activated p38 and c-Jun, but not JNK, another possible downstream target of ASK1. Furthermore, we examined the relationship between phosphatidylinositol 3-kinase (PI3-K) and ASK1. The addition of LY294002, a specific inhibitor of PI3-K, enhanced the ASK1 activity. These results indicate that ASK1 works downstream of PI3-K to regulate the p38-c-Jun pathway and apoptosis in cultured cerebellar granule neurons.",
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Apoptosis-signal regulating kinase-1 is involved in the low potassium-induced activation of p38 mitogen-activated protein kinase and c-Jun in cultured cerebellar granule neurons. / Yamagishi, Satoru; Yamada, Masashi; Koshimizu, Hisatsugu; Takai, Satomi; Hatanaka, Hiroshi; Takeda, Kohsuke; Ichijo, Hidenori; Shimoke, Koji; Ikeuchi, Toshihiko.

In: Journal of Biochemistry, Vol. 133, No. 6, 01.06.2003, p. 719-724.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apoptosis-signal regulating kinase-1 is involved in the low potassium-induced activation of p38 mitogen-activated protein kinase and c-Jun in cultured cerebellar granule neurons

AU - Yamagishi, Satoru

AU - Yamada, Masashi

AU - Koshimizu, Hisatsugu

AU - Takai, Satomi

AU - Hatanaka, Hiroshi

AU - Takeda, Kohsuke

AU - Ichijo, Hidenori

AU - Shimoke, Koji

AU - Ikeuchi, Toshihiko

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Previously, we reported that p38, which belongs to the mitogen-activated protein kinase (MAPK) superfamily, has an important role in the induction of apoptosis of cultured cerebellar granule neurons. However, the molecular mechanisms upstream of p38 activation remain unclear. Apoptosis signal-regulating kinase-1 (ASK1), a MAPK kinase kinase (MAPKKK) protein, is known to activate both c-Jun N-terminal kinase (JNK) and p38 via MAPK kinase (MKK) 4/7 and MKK3/6, respectively. Here, we examined whether ASK1 is involved in the activation of p38 in the low potassium (LK)-induced apoptosis of cerebellar granule neurons. We found that ASK1 was activated after a change to LK medium. In addition, the expression of ASK1-KM, a dominant-negative form of ASK1, using an adenovirus system was found to inhibit the activation of p38 and c-Jun and to prevent apoptosis. On the other hand, the expression of ASK1-ΔN, a constitutively active form of ASK1, activated p38 and c-Jun, but not JNK, another possible downstream target of ASK1. Furthermore, we examined the relationship between phosphatidylinositol 3-kinase (PI3-K) and ASK1. The addition of LY294002, a specific inhibitor of PI3-K, enhanced the ASK1 activity. These results indicate that ASK1 works downstream of PI3-K to regulate the p38-c-Jun pathway and apoptosis in cultured cerebellar granule neurons.

AB - Previously, we reported that p38, which belongs to the mitogen-activated protein kinase (MAPK) superfamily, has an important role in the induction of apoptosis of cultured cerebellar granule neurons. However, the molecular mechanisms upstream of p38 activation remain unclear. Apoptosis signal-regulating kinase-1 (ASK1), a MAPK kinase kinase (MAPKKK) protein, is known to activate both c-Jun N-terminal kinase (JNK) and p38 via MAPK kinase (MKK) 4/7 and MKK3/6, respectively. Here, we examined whether ASK1 is involved in the activation of p38 in the low potassium (LK)-induced apoptosis of cerebellar granule neurons. We found that ASK1 was activated after a change to LK medium. In addition, the expression of ASK1-KM, a dominant-negative form of ASK1, using an adenovirus system was found to inhibit the activation of p38 and c-Jun and to prevent apoptosis. On the other hand, the expression of ASK1-ΔN, a constitutively active form of ASK1, activated p38 and c-Jun, but not JNK, another possible downstream target of ASK1. Furthermore, we examined the relationship between phosphatidylinositol 3-kinase (PI3-K) and ASK1. The addition of LY294002, a specific inhibitor of PI3-K, enhanced the ASK1 activity. These results indicate that ASK1 works downstream of PI3-K to regulate the p38-c-Jun pathway and apoptosis in cultured cerebellar granule neurons.

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