Genetic studies in Arabidopsis have provided evidence that ethylene perception in plants is mediated by a family of receptors, including the ETR1 gene product. The ETR1 gene encodes a protein with homology to the twocomponent His kinase regulators that control a variety of signaling cascades in prokaryotic systems and some eukaryotic systems (Chang et al., 1993). While ETR1 was the first ethylene receptor to be identified in plants (Bleecker et al., 1988), additional screens for ethylene-insensitive seedlings and cloning by sequence similarity indicate that additional genes mediate ethylene sensitivity in Arabidopsis (Hua et al., 1995(Hua et al., , 1998 Sakai et al., 1998). The ERS1, ETR2, EIN4, and ERS2 genes all show a high degree of sequence similarity to ETR1 and appear to comprise a small family of ethylene receptors. Dominant point mutations that confer ethylene insensitivity in planta have been isolated in the ETR1, ETR2, and EIN4 genes, and all of these mutations are located within the putative transmembrane domains in the N-termini of these genes. Similar mutations introduced into ERS1 and ERS2 also confer dominant insensitivity when transformed into Arabidopsis plants (Hua et al., 1995(Hua et al., , 1998. These studies indicate that a single mutation in any one of these five genes is sufficient to render plants insensitive to ethylene throughout the plant.Subsequent biochemical experiments have confirmed that the ETR1 gene encodes an ethylene receptor. The N-terminal hydrophobic domain of the ETR1 protein binds ethylene with high affinity when expressed in yeast (Schaller and Bleecker, 1995). The ethylene-binding (sensor) domain of ETR1 consists of three putative membranespanning subdomains that are modeled as alpha helices (Rodriguez et al., 1999). Notably, the etr1-1 mutation in subdomain 2 abolishes ethylene binding by the yeastexpressed protein (Schaller and Bleecker, 1995). Biochemical studies demonstrated that a copper ion in the N-terminal hydrophobic domain of ETR1 is required for ethylene binding, and that the etr1-1 mutation abolishes the capacity of the receptor to coordinate this ion (Rodriguez et al., 1999).Genetic evidence indicates that the ETR1 receptor family signals through the Raf-like kinase CTR1. Loss-of-function mutations in CTR1 show a constitutive triple-response phenotype, indicating that CTR1 acts as a negative regulator of ethylene-response pathways (Kieber et al., 1993). Recently, Hua and Meyerowitz (1998) demonstrated that combining loss-of-function mutants in three or more members of the ETR1 family also results in plants with a constitutive ethylene-response phenotype. These results favor a model for receptor signaling in which the ETR1 receptor family acts in conjunction with CTR1 to suppress response pathways in the absence of ethylene. Ethylene binding would convert receptors to a non-signaling state, resulting in derepression of the response pathway.Based on the concept of ethylene as a negative regulator of the ETR1 receptor family, we hypothesized that domin...