Protein kinase and phosphatase signaling in Mycobacterium tuberculosis physiology and pathogenesis

Biochemical and Spatial Coincidence in the Provisional Ser/Thr Protein Kinase Interaction Network of Mycobacterium tuberculosis*

“…These precedents suggest that the efficiency of kinase reactions in vitro can provide candidates for the physiological interactions that comprise signaling networks in vivo. The regulation of the bacterial STPKs by activation loop phosphorylation (23,24,35) and the discovery of functional kinase cross-phosphorylations in M. tuberculosis and M. xanthus (15,33) suggested that bacterial STPKs may form a hierarchical network that could be defined based on the kinetic efficiency with which each kinase modified the others (36).…”

Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity

“…Later work also described one of the substrates of PknD, osmosensory protein A (OprA), to be up-regulated in the presence of increasing extracellular osmolarity and to enable adaptation through modifying peptidoglycan thickness (55,56). Several other enzymes involved in the synthesis of cell wall components are also substrates of PknD, including malonyl-CoA:acyl carrier protein transacylase (FabD) and the ␤-ketoacyl-acyl carrier protein synthases KasA and KasB (39).…”

“…EGT could not be detected in extracts prepared from the ⌬egtD mutant, whereas both the wild-type and complemented strains synthesized considerable amounts of EGT (Fig. 3D) (39). Screening of a set of M. tuberculosis STPKs for their ability to phosphorylate purified EgtD identified PknA, PknB, PknD, and PknK as kinases capable of phosphorylating EgtD (Fig.…”

An Integration of Interdisciplinary Translational Research in Anti-TB Drug Discovery: Out of the University Research Laboratories to Combat Mycobacterium tuberculosis

“…All Rpfs have some sequence variation at the N-and C-termini conferring the possibility of recognizing different substrates and interacting with other proteins involved in their regulation [11]. In mycobacteria, the serine/threonine protein kinases (STPKs) are responsible for the regulation of different cellular processes including cell development, survival inside macrophages, stress responses and host-pathogen interactions [12]. A serine/threonine protein kinase, PrkC in Bacillus subtilis [13] (a homologue of the M. tuberculosis PknB), has been reported to act as an effective signal leading to spore germination, which is considered to be a similar physiological process to mycobacterial resuscitation [14].…”