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RPM-1 Uses Both Ubiquitin Ligase and Phosphatase-Based Mechanisms to Regulate DLK-1 during Neuronal Development


The molecular mechanisms that govern formation of functional synaptic connections are central to brain development and function. We have used the nematode C. elegans to explore the mechanism of how the intracellular signaling protein RPM-1 regulates neuronal development. Using a combination of proteomic, genetic, transgenic, and biochemical approaches we have shown that RPM-1 functions through a PP2C phosphatase, PPM-2, to regulate the activity of a MAP3 kinase, DLK-1. Our results indicate that a combination of PPM-2 phosphatase activity and RPM-1 ubiquitin ligase activity inhibit DLK-1.


Vyšlo v časopise: RPM-1 Uses Both Ubiquitin Ligase and Phosphatase-Based Mechanisms to Regulate DLK-1 during Neuronal Development. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004297
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004297

Souhrn

The molecular mechanisms that govern formation of functional synaptic connections are central to brain development and function. We have used the nematode C. elegans to explore the mechanism of how the intracellular signaling protein RPM-1 regulates neuronal development. Using a combination of proteomic, genetic, transgenic, and biochemical approaches we have shown that RPM-1 functions through a PP2C phosphatase, PPM-2, to regulate the activity of a MAP3 kinase, DLK-1. Our results indicate that a combination of PPM-2 phosphatase activity and RPM-1 ubiquitin ligase activity inhibit DLK-1.


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