Signal transduction regulated by MAP kinase cascades

(1)丝裂原活化蛋白激酶(MAPK)通路可以在MAPK激活步骤中被MAPK磷酸酶(MKP)家族成员灭活。秀丽线虫VHP-1基因编码一种MKP，它优先作用于JNK和p38 MAPK。VHP-1负性调节由MLK-1(MAPKKK)、MEK-1(MAPKK)和KGB-1(JNK-like MAPK)组成的JNK样MAPK通路，参与对重金属的应激反应。这些结果表明，VHP-1在KGB-1 MAPK通路调控的应激反应的整合和微调中起着关键作用。(2)Kinesin-1是由Kinesin重链(KHC)和Kinesin轻链(KLC)组成的异源四聚体。线虫基因组有一个由UNC-116基因编码的KHC和两个由KLC-1和KLC-2基因编码的KLC。我们在这里证明了UNC-116/KHC和KLC-2形成了与传统Kinesin-1同源的复合体。KLC-2还与线虫JIP3/JSAP1 JNK信号支架蛋白和UNC-14 Run结构域蛋白UNC-16结合。KLC-2和UNC-16共同定位于神经细胞。UNC-16和UNC-14的定位依赖于Kinesin-1(UNC-116和KLC-2)。此外，UNC-16、KLC-2、UNC-116和UNC-14的突变都会改变含有突触小泡标记的货物的定位。双突变分析与这四个基因在同一途径上的功能一致。我们的数据支持一种模型，在该模型中，UNC-16和UNC-14共同作为Kinesin-1货物和突触小泡成分运输或定位的调节器发挥作用。

(1)Mitogen-activated protein kinase(MAPK) cascades can be inactivated at the MAPK activation step by members of the MAPK phosphatase(MKP) family. The Caenorhabditis elegans vhp-1 gene encodes an MKP that acts preferentially on the JNK and p38 MAPKs. VHP-1 negatively regulates a JNK-like MAPK pathway composed of MLK-1 (MAPKKK), MEK-1 (MAPKK) and KGB-1 (JNK-like MAPK) that is involved in a stress response to heavy metals. These results suggest that VHP-1 plays a pivotal role in the integration and fine-tuning of the stress response regulated by the KGB-1 MAPK pathway.(2)Kinesin-1 is a heterotetramer composed of kinesin heavy chain(KHC) and kinesin light chain(KLC). The C.elegans genome has a single KHC, encoded by unc-116 gene, and two KLCs, encoded by the klc-1 and klc-2 genes. We show here that UNC-116/KHC and KLC-2 form a complex orthologous to conventional kinesin-1. KLC-2 also binds UNC-16,the C.elegans JIP3/JSAP1 JNK-signaling scaffold protein, and the UNC-14 RUN domain protein. KLC-2 and UNC-16 co-localize in neuronal cells. The localization of UNC-16 and UNC-14 depends on kinesin-1 (UNC-116 and KLC-2). Furthermore, mutations in unc-16,klc-2,unc-116, and unc-14 all alter the localization of cargos containing synaptic vesicle markers. Double mutant analysis is consistent with these four genes functioning in the same pathway. Our data support a model whereby UNC-16 and UNC-14 function together as kinesin-1 cargos and regulators for the transport or localization of synaptic vesicle components.