Signal transduction networks regulated by MAP kinase cascades

1.渗透应激激活MAPK，包括JNK和p38，其在细胞应激反应中起重要作用。TAK 1是MAPKKK家族的成员，可以激活JNK和p38。TAK 1还可以激活IKK，从而导致NF-κ B激活。我们发现，TAK 1是必不可少的渗透胁迫诱导的JNK激活，但不是p38激活的唯一介质。此外，我们还发现，尽管TAK 1在渗透胁迫下被高度激活，但它不能诱导NF-κ B的激活。这些结果表明，TAK 1活性以某种方式被调节为在渗透应激信号传导中特异性地起作用，导致JNK而不是IKK的激活。为了阐明这种调节的机制，我们筛选了潜在的TAK 1结合蛋白。我们发现TAO 2与TAK 1结合，可以抑制TAK 1介导的NF-κ B的活化，但不能抑制JNK的活化。我们观察到TAO 2可以干扰TAK 1和IKK之间的相互作用，从而可能调节TAK 1的功能. ERK MAPK激活的不同模式（持续或短暂）对于培养细胞中的细胞命运决定至关重要。我们发现，ERK活性的持续时间有助于建立背腹图案在非洲爪蟾中胚层形成。虽然ERK的瞬时激活足以诱导泛中胚层基因Xbra的表达，但持续的ERK激活对于背侧中胚层基因Chd的表达是必需的。一致的是，在早期原肠胚，ERK的长期激活发生在背中胚层，其中Xbra和Chd都表达。因此，非洲爪蟾Fos蛋白积累在背中胚层。此外，我们发现，xFos可以作为一个分子传感器的ERK信号转导的持续时间在非洲爪蟾胚胎。

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.