RGD Reference Report - Translocation of PKC-betaII is mediated via RACK-1 in the neuronal cells following dioxin exposure. - Rat Genome Database

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Translocation of PKC-betaII is mediated via RACK-1 in the neuronal cells following dioxin exposure.

Authors: Lee, HG  Kim, SY  Choi, EJ  Park, KY  Yang, JH 
Citation: Lee HG, etal., Neurotoxicology. 2007 Mar;28(2):408-14. Epub 2006 May 5.
RGD ID: 5131886
Pubmed: (View Article at PubMed) PMID:16797713
DOI: Full-text: DOI:10.1016/j.neuro.2006.04.007

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to induce neurotoxic effects. However, the mechanism of TCDD-mediated signaling pathways and its possible molecular targets in neurons remains unknown. In this study, we analyzed effects of TCDD on neurofilament subunits, receptor for activated C kinase-1 (RACK-1), and PKC-betaII activity in developing neuronal cells. TCDD induced a significant increase of RACK-1, an adaptor protein for protein kinase C (PKC), in cerebellar granule cells in both dose- and time-dependent manner, indicating that RACK-1 is a sensitive molecular target in neuronal cells for TCDD exposure. TCDD induced a dose-dependent translocation of PKC-betaII from cytosol to membrane fractions. However, when RACK-1 induction was blocked by antisense oligonucleotide or alpha-naphthoflavone, Ah receptor (AhR) inhibitor, the translocation of PKC-betaII was inhibited. Our data suggests that TCDD activates PKC-betaII via RACK-1 in an AhR-dependent manner. This is the first report identifying RACK-1 as a target molecule involved in TCDD-mediated signaling pathways. TCDD exposure also increased the level of neurofilament-H mRNA. These results suggest that identification of target molecules may contribute to improve our understanding of TCDD-mediated signaling pathway and the risk assessment of TCDD-induced neurotoxicities.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Prkcb  (protein kinase C, beta)
Rack1  (receptor for activated C kinase 1)


Additional Information