Document Detail

A novel FERM domain including guanine nucleotide exchange factor is involved in Rac signaling and regulates neurite remodeling.
MedLine Citation:
PMID:  12351724     Owner:  NLM     Status:  MEDLINE    
The Rho family of small GTPases, key regulators of the actin cytoskeleton in eukaryotic cells from yeast to human, is implicated in the control of neuronal morphology. Guanine nucleotide exchange factors (GEFs) are upstream positive regulators of Rho GTPases and integrate extracellular signaling for appropriate activation of Rho GTPases at specific subcellular regions. Here we describe the identification of a novel Dbl family GEF for Rho GTPases in Homo sapiens and Mus musculus. It contains a tandem Dbl homology-pleckstrin homology domain and FERM domain, characteristic of the plasma membrane proteins linker. This gene, termed FERM domain including RhoGEF (FIR), was abundantly expressed in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FIR was found to activate the biochemical pathway specific for Rac1 but not for RhoA or Cdc42. Ectopic expression of FIR in the cortical neurons resulted in significantly shortened neurites and excessive growth cones, presumably mediated by Rac1. These results suggest that FIR may regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac.
Tateki Kubo; Toshihide Yamashita; Atsushi Yamaguchi; Hideki Sumimoto; Ko Hosokawa; Masaya Tohyama
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  22     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-27     Completed Date:  2002-10-24     Revised Date:  2006-09-19    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8504-13     Citation Subset:  IM    
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
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MeSH Terms
3T3 Cells / metabolism
COS Cells
Cells, Cultured
Cerebral Cortex / cytology,  metabolism
Growth Cones / metabolism,  ultrastructure
Guanine Nucleotide Exchange Factors / genetics,  metabolism*
Hippocampus / cytology,  metabolism
Kidney / cytology,  metabolism
Molecular Sequence Data
Neurites / metabolism*,  ultrastructure
Neurons / cytology,  metabolism
Organ Specificity
Protein Structure, Tertiary / physiology
RNA, Messenger / analysis,  biosynthesis
Sequence Homology, Amino Acid
Signal Transduction / physiology
cdc42 GTP-Binding Protein / metabolism
rac1 GTP-Binding Protein / metabolism*
rho GTP-Binding Proteins / metabolism*
rhoA GTP-Binding Protein / metabolism
Reg. No./Substance:
0/FARP2 protein, human; 0/Guanine Nucleotide Exchange Factors; 0/RNA, Messenger; EC GTP-Binding Protein; EC GTP-Binding Protein; EC GTP-Binding Proteins; EC GTP-Binding Protein

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

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