Signal transduction regulated by MAP kinase cascades

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(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.