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.
Mesh Terms:
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
Nature
Date: Sep. 16, 1999
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