title: Multiple signals modulate the activity of the complex sensor kinase TodS.
abstract: The reason for the existence of complex sensor kinases is little understood but thought to lie in the capacity to respond to multiple signals. The complex, seven-domain sensor kinase TodS controls in concert with the TodT response regulator the expression of the toluene dioxygenase pathway in Pseudomonas putida F1 and DOT-T1E. We have previously shown that some aromatic hydrocarbons stimulate TodS activity whereas others behave as antagonists. We show here that TodS responds in addition to the oxidative agent menadione. Menadione but no other oxidative agent tested inhibited TodS activity in vitro and reduced PtodX expression in vivo. The menadione signal is incorporated by a cysteine-dependent mechanism. The mutation of the sole conserved cysteine of TodS (C320) rendered the protein insensitive to menadione. We evaluated the mutual opposing effects of toluene and menadione on TodS autophosphorylation. In the presence of toluene, menadione reduced TodS activity whereas toluene did not stimulate activity in the presence of menadione. It was shown by others that menadione increases expression of glucose metabolism genes. The opposing effects of menadione on glucose and toluene metabolism may be partially responsible for the interwoven regulation of both catabolic pathways. This work provides mechanistic detail on how complex sensor kinases integrate different types of signal molecules.
authors.affiliation: Department of Environmental Protection, Consejo Superior de Investigaciones Científicas, Estación Experimental del Zaidín, C/ Prof. Albareda 1, Granada, 18008, Spain.
authors.forename: Hortencia
authors.initials: H
authors.lastname: Silva-Jiménez
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Ortega
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Fontana
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Ramos
authors.forename: Tino
authors.initials: T
authors.lastname: Krell
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D016958:Pseudomonas putida / Q000201:enzymology* / Q000235:genetics; D014812:Vitamin K / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D014812:Vitamin K; D011494:Protein Kinases; C104649:TodS protein, Pseudomonas putida; D003545:Cysteine; C023885:menadiol