QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online July 2, 2008

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?

PKC opens up in ataxia

The neurodegenerative disorder spinocerebellar ataxia type 14 (SCA14) is caused by mutations in PKC, which is the neuron-specific isoform of the PKC family. Twenty-three SCA14-associated mutations of PKC have been reported; most of these fall within the C1B regulatory subdomain, but their effect on PKC function is not well understood. On page 2339, Eric Reits and colleagues analyse the activity of three SCA14-associated mutants of PKC, each of which harbours a point mutation in the C1B subdomain. The authors show that GFP-tagged versions of all three mutant proteins localise to the cytoplasm in HeLa cells, as wild-type PKC does. However, when cells are treated with phorbol ester (which activates PKC by binding to the C1 domain), the three mutants redistribute to the plasma membrane more rapidly than the wild-type protein. In addition, the authors show that the efficiency of intramolecular FRET is reduced in the three PKC point mutants, which might indicate that they adopt a more open conformation in which the C1 domain is more accessible to phorbol ester. Notably, all three mutants have reduced kinase activity, and cells that express the mutant proteins exhibit reduced phosphorylation and nuclear accumulation of ERK2. These results shed light on the role of PKC in SCA14 pathogenesis.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

PKC mutations in spinocerebellar ataxia type 14 affect C1 domain accessibility and kinase activity leading to aberrant MAPK signaling

Dineke S. Verbeek, Joachim Goedhart, Laurie Bruinsma, Richard J. Sinke, and Eric A. Reits
JCS 2008 121: 2339-2349. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?