Signal transduction regulated by MAP kinase cascades

(1)丝裂原活化蛋白激酶（MAPK）级联可被MAPK磷酸酶（MKP）家族成员在MAPK激活步骤中失活。秀丽隐杆线虫vhp-1基因编码的MKP优先作用于JNK和p38 MAPKs。VHP-1负调控由MLK-1 （MAPKKK）、MEK-1 （MAPKK）和KGB-1 （JNK-like MAPK）组成的jnk样MAPK通路，该通路参与重金属胁迫反应。这些结果表明，VHP-1在整合和微调由KGB-1 MAPK通路调节的应激反应中起着关键作用。(2) kinesin -1是由kinesin重链（KHC）和kinesin轻链（KLC）组成的异四聚体。秀丽隐杆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。我们在这里发现UNC-116/KHC和KLC-2形成一个与传统的激酶-1同源的复合体。KLC-2还结合UNC-16、秀丽隐杆线虫jp3 /JSAP1 jnk信号支架蛋白和UNC-14 RUN结构域蛋白。KLC-2和UNC-16在神经元细胞中共定位。UNC-16和UNC-14的定位依赖于激酶1 （UNC-116和KLC-2）。此外，unc-16、klc-2、unc-116和unc-14的突变都改变了含有突触囊泡标记物的货物的定位。双突变分析与这四个基因在同一途径中起作用是一致的。我们的数据支持一个模型，即UNC-16和UNC-14共同作为驱动蛋白-1的货物和调节突触囊泡成分的运输或定位。

(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.