Ethylene insensitive 2(EIN2),an integral membrane protein of the ER network,has been identified as the central regulator of the ethylene signaling pathway.Still,the mechanism by which the ethylene signal is transferred from the receptors to EIN2 has not been solved yet.Here,we show that protein phosphorylation is a key mechanism to control the interaction of EIN2 and the receptors.In vivo and in vitro fluorescence studies reveal that the kinase domain of the receptors is essential for the interaction.Cyanide,an ethylene agonist,which is known to reduce auto-phosphorylation of the ethylene receptor ethylene resistant 1(ETR1)or a mutation in the kinase domain of ETR1 that prevents autophosphorylation (H353A),increases the affinity of the receptors for EIN2.On the other hand,mimicking permanent auto-phosphorylation of ETR1 as in the mutant H353E releases the EIN2-ETR1 interaction from the control by the plant hormone.Based on our data,we propose a novel model on the integration of EIN2 in the ethylene signaling cascade.