EPS8 and E3B1 transduce signals from Ras to Rac.
The small guanine nucleotide (GTP)-binding protein Rac regulates mitogen-induced cytoskeletal changes and c-Jun amino-terminal kinase (JNK), and its activity is required for Ras-mediated cell transformation. Epistatic analysis placed Rac as a key downstream target in Ras signalling; however, the biochemical mechanism regulating the cross-talk among these small GTP-binding proteins remains to be elucidated. Eps8 (relative molecular mass 97,000) is a substrate of receptors with tyrosine kinase activity which binds, through its SH3 domain, to a protein designated E3b1/Abi-1. Here we show that Eps8 and E3b1/Abi-1 participate in the transduction of signals from Ras to Rac, by regulating Rac-specific guanine nucleotide exchange factor (GEF) activities. We also show that Eps8, E3b1 and Sos-1 form a tri-complex in vivo that exhibits Rac-specific GEF activity in vitro. We propose a model in which Eps8 mediates the transfer of signals between Ras and Rac, by forming a complex with E3b1 and Sos-1.
Pubmed ID: 10499589 RIS Download
3T3 Cells | Adaptor Proteins, Signal Transducing | Animals | COS Cells | Carrier Proteins | Cloning, Molecular | Cytoskeletal Proteins | GTP Phosphohydrolases | GTP-Binding Proteins | Genetic Vectors | Guanine Nucleotide Exchange Factors | Guanosine Triphosphate | Intracellular Signaling Peptides and Proteins | Mice | Protein Binding | Proteins | Signal Transduction | rac GTP-Binding Proteins | ras Guanine Nucleotide Exchange Factors | ras Proteins