Document Detail

Identification of a negative regulatory region for the exchange activity and characterization of T332I mutant of Rho guanine nucleotide exchange factor 10 (ARHGEF10).
MedLine Citation:
PMID:  21719701     Owner:  NLM     Status:  MEDLINE    
The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1-332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant.
Taro Chaya; Satoshi Shibata; Yasunori Tokuhara; Wataru Yamaguchi; Hiroshi Matsumoto; Ichiro Kawahara; Mikihiko Kogo; Yoshiharu Ohoka; Shinobu Inagaki
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-30
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-22     Completed Date:  2011-10-18     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29511-20     Citation Subset:  IM    
Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
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MeSH Terms
Amides / pharmacology
Amino Acid Substitution
Enzyme Inhibitors / pharmacology
Guanine Nucleotide Exchange Factors / genetics,  metabolism*
HEK293 Cells
HeLa Cells
Mutation, Missense*
Myelin Sheath / genetics,  metabolism*
Peptide Mapping / methods
Peripheral Nerves / metabolism*
Protein Structure, Tertiary
Pyridines / pharmacology
rho-Associated Kinases / genetics,  metabolism
rhoA GTP-Binding Protein / genetics,  metabolism
Reg. No./Substance:
0/ARHGEF10 protein, human; 0/Amides; 0/Enzyme Inhibitors; 0/Guanine Nucleotide Exchange Factors; 0/Pyridines; 124671-05-2/RHOA protein, human; 138381-45-0/Y 27632; EC Kinases; EC GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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