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Publication : DCX, a new mediator of the JNK pathway.

First Author  Gdalyahu A Year  2004
Journal  EMBO J Volume  23
Issue  4 Pages  823-32
PubMed ID  14765123 Mgi Jnum  J:88445
Mgi Id  MGI:3033281 Doi  10.1038/sj.emboj.7600079
Citation  Gdalyahu A, et al. (2004) DCX, a new mediator of the JNK pathway. EMBO J 23(4):823-32
abstractText  Mutations in the X-linked gene DCX result in lissencephaly in males, and abnormal neuronal positioning in females, suggesting a role for this gene product during neuronal migration. In spite of several known protein interactions, the involvement of DCX in a signaling pathway is still elusive. Here we demonstrate that DCX is a substrate of JNK and interacts with both c-Jun N-terminal kinase (JNK) and JNK interacting protein (JIP). The localization of this signaling module in the developing brain suggests its functionality in migrating neurons. The localization of DCX at neurite tips is determined by its interaction with JIP and by the interaction of the latter with kinesin. DCX is phosphorylated by JNK in growth cones. DCX mutated in sites phosphorylated by JNK affected neurite outgrowth, and the velocity and relative pause time of migrating neurons. We hypothesize that during neuronal migration, there is a need to regulate molecular motors that are working in the cell in opposite directions: kinesin (a plus-end directed molecular motor) versus dynein (a minus-end directed molecular motor).
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