The nucleotide exchange factor Cdc24p may be regulated by auto-inhibition.
Site-specific activation of the Rho-type GTPase Cdc42p by its guanine-nucleotide exchange factor (GEF) Cdc24p is critical for the establishment of cell polarity. Here we show that binding of Cdc24p to the small GTPase Rsr1p/Bud1p is required for its recruitment to the incipient bud site. Rsr1p/Bud1p binds to the CH-domain of ... Cdc24p, which is essential for its function in vivo. We have identified a cdc24-mutant allele, which is specifically defective for bud-site selection. Our results suggest that Cdc24p is auto-inhibited by an intramolecular interaction with its carboxy-terminal PB1-domain. Rsr1p/Bud1p appears to activate the GEF activity of Cdc24p in vivo, possibly by triggering a conformational change that dissociates the PB1-domain from its intramolecular binding site. Genetic experiments suggest that Bem1p functions as a positive regulator of Cdc24p by binding to the PB1-domain of Cdc24p, thereby preventing its re-binding to the intramolecular inhibitory site. Taken together, our results support a two-step molecular mechanism for the site-specific activation of Cdc24p, which involves Rsr1p/Bud1p and the adaptor protein Bem1p.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Alleles, Cell Cycle Proteins, Cell Membrane, Gene Expression Regulation, Fungal, Guanine Nucleotide Exchange Factors, Mutation, Protein Binding, Protein Structure, Tertiary, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, rab GTP-Binding Proteins
Adaptor Proteins, Signal Transducing, Alleles, Cell Cycle Proteins, Cell Membrane, Gene Expression Regulation, Fungal, Guanine Nucleotide Exchange Factors, Mutation, Protein Binding, Protein Structure, Tertiary, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, rab GTP-Binding Proteins
EMBO J.
Date: Mar. 10, 2004
PubMed ID: 14988726
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