Signal transduction networks regulated by MAP kinase cascades

1. 渗透胁迫激活MAPKs，包括JNK和p38，它们在细胞应激反应中起重要作用。TAK1是MAPKKK家族的成员，可以激活JNK和p38。TAK1也可以激活IKK，从而导致NF-KB的激活。我们发现TAK1对于渗透胁迫诱导的JNK激活是必需的，但不是p38激活的唯一介质。此外，我们发现虽然TAK1在渗透胁迫下被高度激活，但它不能诱导NF-_KB的激活。这些结果表明，TAK1活性以某种方式被调节为渗透胁迫信号的特异性功能，导致JNK的激活而不是IKK的激活。为了阐明这种调节的机制，我们筛选了潜在的tak1结合蛋白。我们发现TAO2与TAK1结合，可以抑制TAK1介导的NF-_KB的激活，但不能抑制JNK的激活。我们观察到TAO2可以干扰TAK1和IKK之间的相互作用，从而可能调节TAK1的功能。ERK MAPK激活的不同模式，持续或短暂，对培养细胞的细胞命运决定至关重要。我们发现ERK活动的持续时间有助于非洲爪蟾中胚层形成过程中背-腹侧模式的建立。虽然ERK的短暂激活足以诱导泛中胚层基因Xbra的表达，但ERK的持续激活对于中胚层背侧基因Chd的表达是必要的。与此一致的是，在原肠期早期，ERK的长期激活发生在Xbra和Chd均表达的背中胚层。因此，非洲爪蟾Fos蛋白在背中胚层中积累。此外，我们发现xfo可以作为爪蟾胚胎中ERK信号传导持续时间的分子传感器。

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.