The ubiquitin-like protein LC3 regulates the Rho-GEF activity of AKAP-Lbc.

Details

Serval ID
serval:BIB_A58F8BEA4707
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The ubiquitin-like protein LC3 regulates the Rho-GEF activity of AKAP-Lbc.
Journal
Journal of Biological Chemistry
Author(s)
Baisamy L., Cavin S., Jurisch N., Diviani D.
ISSN
1083-351X (Electronic)
ISSN-L
0021-9258
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
284
Number
41
Pages
28232-28242
Language
english
Abstract
AKAP-Lbc is a member of the A-kinase anchoring protein (AKAP) family that has been recently associated with the development of pathologies, such as cardiac hypertrophy and cancer. We have previously demonstrated that, at the molecular level, AKAP-Lbc functions as a guanine nucleotide exchange factor (GEF) that promotes the specific activation of RhoA. In the present study, we identified the ubiquitin-like protein LC3 as a novel regulatory protein interacting with AKAP-Lbc. Mutagenesis studies revealed that LC3, through its NH(2)-terminal alpha-helical domain, interacts with two binding sites located within the NH(2)-terminal regulatory region of AKAP-Lbc. Interestingly, LC3 overexpression strongly reduced the ability of AKAP-Lbc to interact with RhoA, profoundly impairing the Rho-GEF activity of the anchoring protein and, as a consequence, its ability to promote cytoskeletal rearrangements associated with the formation of actin stress fibers. Moreover, AKAP-Lbc mutants that fail to interact with LC3 show a higher basal Rho-GEF activity as compared with the wild type protein and become refractory to the inhibitory effect of LC3. This suggests that LC3 binding maintains AKAP-Lbc in an inactive state that displays a reduced ability to promote downstream signaling. Collectively, these findings provide evidence for a previously uncharacterized role of LC3 in the regulation of Rho signaling and in the reorganization of the actin cytoskeleton.
Keywords
A Kinase Anchor Proteins/genetics, A Kinase Anchor Proteins/metabolism, Animals, Cell Line, Guanine Nucleotide Exchange Factors/genetics, Guanine Nucleotide Exchange Factors/metabolism, Humans, Mice, Microtubule-Associated Proteins/genetics, Microtubule-Associated Proteins/metabolism, Models, Molecular, NIH 3T3 Cells, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins/metabolism, Recombinant Fusion Proteins/genetics, Recombinant Fusion Proteins/metabolism, Signal Transduction/physiology, Two-Hybrid System Techniques
Pubmed
Web of science
Open Access
Yes
Create date
18/09/2009 9:01
Last modification date
03/11/2020 9:26
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