tailieunhanh - Báo cáo khoa học: EmbR, a regulatory protein with ATPase activity, is a substrate of multiple serine⁄threonine kinases and phosphatase in Mycobacterium tuberculosis

Phosphorylation of the mycobacterial transcriptional activator, EmbR, is essential for transcriptional regulation of theembCABoperon encoding cell wall arabinosyltransferases. This signaling pathway eventually affects the resistance to ethambutol (a frontline antimycobacterial drug) and the cell wall Lipoarabinomannan⁄Lipomannan ratio (an important determinant for averting the host immune response). | ềFEBS Journal EmbR a regulatory protein with ATPase activity is a substrate of multiple serine threonine kinases and phosphatase in Mycobacterium tuberculosis Kirti Sharma1 Meetu Gupta1 Ananth Krupa Narayanaswamy Srinivasan2 and Yogendra Singh1 1 Institute of Genomics and Integrative Biology Delhi India 2 Molecular Biophysics Unit Indian Institute of Science Bangalore Keywords ATPase kinase phosphatase Mycobacterium tuberculosis Correspondence Y. Singh Institute of Genomics and Integrative Biology MallRoad Delhi 110 007 India Fax 91 11 27667471 Tel 91 11 27666156 E-mail ysingh@ Present address Cancer Research UK Clare Hall Laboratories UK Received 23 March 2006 revised 19 April 2006 accepted 24 April 2006 doi Phosphorylation of the mycobacterial transcriptional activator EmbR is essential for transcriptional regulation of the embCAB operon encoding cell wall arabinosyltransferases. This signaling pathway eventually affects the resistance to ethambutol a frontline antimycobacterial drug and the cell wall Lipoarabinomannan Lipomannan ratio an important determinant for averting the host immune response . In this study further biochemical characterization revealed that EmbR as a transcriptional regulator interacts with RNA polymerase and possesses a phosphorylation-dependent ATPase activity that might play a role in forming an open complex between EmbR and RNA polymerase. EmbR was recently shown to be phosphorylated by the cognate mycobacterial serine threonine Ser Thr kinase PknH. Using bioinformatic analysis and in vitro assays we identified additional novel regulators of the signaling pathway leading to EmbR phosphorylation namely the Ser Thr protein kinases PknA and PknB. A previously unresolved question raised by this signaling scheme is the fate of phosphorylated kinases and EmbR at the end of the signaling cycle. Here we show that Mstp a mycobacterial Ser Thr phosphatase antagonizes Ser Thr protein kinase-EmbR .