| Budget Amount *help |
¥51,740,000 (Direct Cost: ¥39,800,000、Indirect Cost: ¥11,940,000)
Fiscal Year 2006: ¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000)
Fiscal Year 2005: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
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| Research Abstract |
1. Osmotic stress activates MAPKs, including JNK and p38, which play important roles in cellular stress responses. TAK1 is a member of the MAPKKK family and can activate JNK and p38. TAK1 can also activate IKK that leads to NF-KB activation. We found that TAK1 is essential for osmotic stress-induced activation of JNK but is not an exclusive mediator of p38 activation. Furthermore, we found that although TAK1 was highly activated upon osmotic stress, it could not induce activation of NF-_KB. These results suggest that TAK1 activity is somehow modulated to function specifically in osmotic stress signaling, leading to the activation of JNK but not of IKK. To elucidate the mechanism underlying this modulation, we screened for potential TAK1-binding proteins. We found that TAO2 associates with TAK1 and can inhibit TAK1-mediated activation of NF-_KB but not of JNK. We observed that TAO2 can interfere with the interaction between TAK1 and IKK and thus may regulate TAK1 function.
2. Distinct modes of ERK MAPK activation, sustained or transient, are critical for cell fate decision in cultured cells. We found that the duration of ERK activity contributes to the establishment of dorsoventral patterning during mesoderm formation in Xenopus. While transient activation of ERK is sufficient to induce expression of the pan-mesodermal gene Xbra, sustained ERK activation is necessary for expression of the dorsal mesodermal gene Chd. Consistently, at early gastrula, prolonged activation of ERK occurs in dorsal mesoderm where both Xbra and Chd are expressed. Consequently, Xenopus Fos protein accumulates in the dorsal mesoderm. Furthermore, we found that xFos can function as a molecular sensor of the duration of ERK signaling in Xenopus embryos.
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