Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

Brain Res Mol Brain Res

Publication Date

10/09/2003

Volume

117

Pages

27 - 38

Keywords

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