Uhl M A, Miller J F
Department of Microbiology and Immunology, School of Medicine, UCLA, Los Angeles, California 90024, USA.
J Biol Chem. 1996 Dec 27;271(52):33176-80. doi: 10.1074/jbc.271.52.33176.
Two-component systems use phosphorylation reactions to regulate stimulus/response pathways. In Bordetella pertussis, a human respiratory pathogen, the infectious cycle of the organism is controlled by the BvgAS two-component system. BvgS has similarities to sensor and response regulator components and is an autophosphorylating kinase that phosphorylates BvgA. BvgA, a response regulator, is a DNA-binding protein that activates virulence gene transcription. Three phosphorylated BvgS domains, the transmitter, receiver, and C terminus, are essential for signal transduction. We now demonstrate that the BvgS transmitter is sufficient for autophosphorylation but is unable to phosphorylate the C terminus or BvgA. The BvgS receiver regulates several phenotypes: dephosphorylation of both the BvgS transmitter and C terminus as well as transfer of a phosphoryl group from the transmitter to the C terminus. Our results indicate that BvgAS signal transduction initiates with autophosphorylation of the transmitter followed by phosphotransfer to the receiver. The phosphorylated receiver can donate to the C terminus or to water. The phosphorylated C terminus is then able to transfer the phosphoryl group to BvgA.
双组分系统利用磷酸化反应来调节刺激/反应途径。在人类呼吸道病原体百日咳博德特氏菌中，该生物体的感染周期由BvgAS双组分系统控制。BvgS与传感器和反应调节子组分具有相似性，是一种自磷酸化激酶，可使BvgA磷酸化。反应调节子BvgA是一种DNA结合蛋白，可激活毒力基因转录。三个磷酸化的BvgS结构域，即传递器、接收器和C末端，对于信号转导至关重要。我们现在证明，BvgS传递器足以进行自磷酸化，但无法使C末端或BvgA磷酸化。BvgS接收器调节多种表型：BvgS传递器和C末端的去磷酸化以及磷酸基团从传递器转移到C末端。我们的结果表明，BvgAS信号转导始于传递器的自磷酸化，随后是磷酸基团转移至接收器。磷酸化的接收器可将磷酸基团转移至C末端或水。然后，磷酸化的C末端能够将磷酸基团转移至BvgA。
