Regulation of transcription by eukaryotic-like serine-threonine kinases and phosphatases in Gram-positive bacterial pathogens

Wright, David P.; Ulijasz, Andrew T.

doi:10.4161/21505594.2014.983404

Cited by 51 publications

(55 citation statements)

References 170 publications

(240 reference statements)

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“…HKs discriminate very strictly amongst cognate RRs and typically phosphorylate only one or two targets. STKs and BY kinases are much less specific, and their actions are more pleiotropic (Shi et al, 2014a;Wright & Ulijasz, 2014). Each STK and BY kinase can phosphorylate a number of different cellular substrates (Mijakovic & Deutscher, 2015), and this relaxed substrate specificity can be traced to a lack of co-evolution between the kinase and its substrates (Shi et al, 2014b).…”

Section: Discussionmentioning

confidence: 99%

“…In the past few years, it has been established that Hankstype serine/threonine kinases (STKs) can phosphorylate TRs in many bacteria and regulate different functions, such as antibiotic resistance, virulence, capsule synthesis and sporulation (Wright & Ulijasz, 2014). The human pathogen Staphylococcus aureus possess two Hanks-type STKs, Stk1 and Stk2, both implicated in regulating virulence and antibiotic resistance (Ohlsen & Donat, 2010;Tamber et al, 2010).…”

Section: Serine/threonine Phosphorylation Of Bacterial Trsmentioning

confidence: 99%

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Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators

et al. 2015

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Reversible phosphorylation of bacterial transcriptional regulators (TRs) belonging to the family of two-component systems (TCSs) is a well-established mechanism for regulating gene expression. Recent evidence points to the fact that reversible phosphorylation of bacterial TRs on other types of residue, i.e. serine, threonine, tyrosine and cysteine, is also quite common. The phosphorylation of the ester type (phospho-serine/threonine/tyrosine) is more stable than the aspartate phosphorylation of TCSs. The kinases which catalyse these phosphorylation events (Hanks-type serine/threonine protein kinases and bacterial protein tyrosine kinases) are also much more promiscuous than the TCS kinases, i.e. each of them can phosphorylate several substrate proteins. As a consequence, the dynamics and topology of the signal transduction networks depending on these kinases differ significantly from the TCSs. Here, we present an overview of different classes of bacterial TR phosphorylated and regulated by serine/threonine and tyrosine kinases. Particular attention is given to examples when serine/threonine and tyrosine kinases interact with TCSs, phosphorylating either the histidine kinases or the response regulators. We argue that these promiscuous kinases connect several signal transduction pathways and serve the role of signal integration. Bacterial two-component systems (TCSs)TCSs are signal transduction devices that were initially discovered in bacteria (Ninfa & Magasani, 1986;Nixon et al., 1986). They play an important role in signal sensing and response to various stimuli, enabling the organisms to adapt to environmental changes. A typical TCS consists of a histidine kinase (HK) and a corresponding response regulator (RR) (Stock et al., 2000;Gao & Stock, 2009). HK usually possesses a highly variable sensor domain and a conserved kinase core. Following environmental stimulus, a signal ligand binds to the sensor domain and results in the autophosphorylation of the kinase core at a conserved histidine residue, at the expense of ATP. Next, the phosphoryl group is transferred from HK to a conserved aspartate in the regulatory domain of the RR. RRs usually contain two domains: a regulatory domain with the conserved phosphorylatable aspartate and a variable effector domain. Phosphorylation activates the effector domain of RRs, triggering the physiological response. As phosphohistidine has a very short half-life in aqueous solutions at neutral pH, in the absence of the environmental signal the system switches itself off very rapidly.Many effector domains of bacterial RRs have DNA-binding capacity. This allows RRs to function as transcriptional regulators (TRs) and consequently change gene transcription when they become phosphorylated. In Escherichia coli, osmoregulation of porin proteins OmpF and OmpC is under transcriptional control of the TCS EnvZ/OmpR. The phosphorylation of OmpR by EnvZ changes its affinity for the promoter region of ompF and ompC, resulting in different transcriptional levels of these genes (Forst et al., 1...

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Section: Discussionmentioning

confidence: 99%

Section: Serine/threonine Phosphorylation Of Bacterial Trsmentioning

confidence: 99%

Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators

et al. 2015

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“…In addition to the paradigm histidine-aspartate phosphotransfer reaction, recent studies have identified serine/threonine kinases capable of phosphorylating RR proteins (reviewed in [112, 113]). Initial in vitro identification of potential phosphorylation sites of Staphylococcus aureus GraR [114] and VraR [115], Mycobacterium tuberculosis DosR and Rv2175c [116–118] , Streptococcus pneumoniae RitR [119] and RR06 [120] and Group A and B Streptococci CovR [121] have been followed by physiological studies of RR06 [120], CovR [122] and B. subtilis WalR [123].…”

Section: Phosphotransfermentioning

confidence: 99%

Molecular Mechanisms of Two-Component Signal Transduction

Zschiedrich

Keidel

Szurmant

2016

Journal of Molecular Biology

415

364

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Two-component systems comprising sensor histidine kinases and response regulator proteins are among the most important players in bacterial and archaeal signal transduction and also occur in reduced numbers in some eukaryotic organisms. Given their importance to cellular survival, virulence and cellular development these systems are among the most scrutinized bacterial proteins. In recent years a flurry of bioinformatics, genetic, biochemical and structural studies have provided detailed insights into many of the molecular mechanisms that underlie the detection of signals and the generation of the appropriate response by two-component systems. Importantly, it has become clear that there is significant diversity in the mechanisms employed by individual systems. This review discusses the current knowledge on common themes and divergences from the paradigm of two-component system signaling. An emphasis is on the information gained by a flurry of recent structural and bioinformatics studies.

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“…Bacteria have a large range of protein kinases, which phosphorylate proteins on several residues (histidine, cysteine, aspartic acid, arginine, serine, threonine and tyrosine), and also a number of phosphoprotein phosphatases for balance and regulation of kinases activity . A number of STPKs are predicted to be soluble cytoplasmic proteins in Gram‐negative bacteria, whereas in Gram‐positive most STPKs are characterized by an intracellular kinase domain (PKinase) connected by a trans ‐membrane linker to a C‐terminal extracellular sensory domain . In pioneering studies, muropeptides produced upon PGN degradation were shown to act as germinants toward B. subtilis spores through activation of the Ser/Thr kinase PrkC .…”

Section: Pgn Degradation and Bacterial Return To Lifementioning

confidence: 99%

Chemistry of Peptidoglycan in Mycobacterium tuberculosis Life Cycle: An off‐the‐wall Balance of Synthesis and Degradation

Squeglia

Ruggiero

Berisio

2017

Chemistry A European J

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The cell wall envelope of mycobacteria is structurally distinct from that of both Gram-positive and Gram-negative bacteria. In Mycobacterium tuberculosis, this cell wall has unique structural features and plays a crucial role in drug resistance and macrophage survival under stress conditions. Peptidoglycan is the major constituent of this cell wall, with an important structural role, giving structural strength, and counteracting the osmotic pressure of the cytoplasm. Synthesis of this complex polymer takes place in three stages that occur at three different locations in the cell, from the cytoplasm to the external side of the cell membrane, where polymerization occurs. A fine balance of peptidoglycan synthesis and degradation is responsible for a plethora of molecular mechanisms which are key to the pathogenicity of M. tuberculosis. Enlargement of mycobacterial cells can occur through the synthesis of new peptidoglycan, autolysis of old peptidoglycan, or a combination of both processes. Here, we discuss the chemical aspects of peptidoglycan synthesis and degradation, in relation to metabolic stages of M. tuberculosis. Going from inside the mycobacterial cytoplasm to outside its membrane, we describe the assembly line of peptidoglycan synthesis and polymerization, and continue with its depolymerization events and their consequences on mycobacterial life and resuscitation from dormancy.

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Regulation of transcription by eukaryotic-like serine-threonine kinases and phosphatases in Gram-positive bacterial pathogens

Cited by 51 publications

References 170 publications

Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators

Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators

Molecular Mechanisms of Two-Component Signal Transduction

Chemistry of Peptidoglycan in Mycobacterium tuberculosis Life Cycle: An off‐the‐wall Balance of Synthesis and Degradation

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