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p190RhoGEF is a large multi-functional protein with guanine nucleotide exchange (GEF) activity. The C-terminal region of p190RhoGEF is a highly interactive domain that binds multiple factors, including proteins with anti-apoptotic activities. We now report that transfection of EGFP-tagged p190RhoGEF protects Neuro 2a cells from stress-induced apoptosis and that anti-apoptotic activity is localized to cytoplasmic retention sequences (CRS-1 and CRS-2) in the C-terminal region of p190RhoGEF. Cytoplasmic retention is conferred to an EGFP fluorescent marker when fused to either CRS-1 or CRS-2. Both cytoplasmic retention and anti-apoptotic activity are lost by deleting CRS-1 and CRS-2 in the p190RhoGEF sequence and can be recovered by restoring either CRS-1 or CRS-2 to the EGFP-tagged sequence. Since the CRS-1 and CRS-2 contain the JIP-1 and 14-3-3 binding sites, we propose that anti-apoptotic activity may be conferred by the binding of p190RhoGEF to JIP-1 or 14-3-3, possibly by altering their interactive properties or nucleocytoplasmic movements. Taken together, our findings support a model whereby multiple interactions of p190RhoGEF confer homeostatic properties to differentiated neurons and may link neuronal homeostasis to the regulation of NF-L expression.


Journal article


Brain Res Mol Brain Res

Publication Date





27 - 38


Animals, Apoptosis, Binding Sites, Blotting, Western, Carrier Proteins, Cell Aggregation, Cell Death, Cell Line, Cytoplasm, DNA-Binding Proteins, GTPase-Activating Proteins, Glutathione Transferase, Green Fluorescent Proteins, Guanine Nucleotide Exchange Factors, In Situ Nick-End Labeling, Intracellular Signaling Peptides and Proteins, Luminescent Proteins, Microscopy, Confocal, Nuclear Proteins, Peptide Fragments, Precipitin Tests, Protein Binding, Proto-Oncogene Proteins c-myc, Repressor Proteins, Sequence Homology, Amino Acid, Transfection, Two-Hybrid System Techniques