Regulatory Interactions of a Virulence-Associated Serine/Threonine Phosphatase-Kinase Pair in Bacillus anthracis
Salika M. Shakir,Katie M. Bryant,Jason L. Larabee,Elaine E. Hamm,Julie A. Lovchik,C. Rick Lyons,Jimmy D. Ballard +6 more
Reads0
Chats0
TLDR
Insight is provided into a previously undescribed Stp/Stk pair in B. anthracis, which is a PP2C phosphatase and dephosphorylates phosphoserine and phosphothreonine residues and can be influenced by BA-Stp1 deph phosphorylation.Abstract:
In the current study, we examined the regulatory interactions of a serine/threonine phosphatase (BA-Stp1), serine/threonine kinase (BA-Stk1) pair in Bacillus anthracis. B. anthracis STPK101, a null mutant lacking BA-Stp1 and BA-Stk1, was impaired in its ability to survive within macrophages, and this correlated with an observed reduction in virulence in a mouse model of pulmonary anthrax. Biochemical analyses confirmed that BA-Stp1 is a PP2C phosphatase and dephosphorylates phosphoserine and phosphothreonine residues. Treatment of BA-Stk1 with BA-Stp1 altered BA-Stk1 kinase activity, indicating that the enzymatic function of BA-Stk1 can be influenced by BA-Stp1 dephosphorylation. Using a combination of mass spectrometry and mutagenesis approaches, three phosphorylated residues, T165, S173, and S214, in BA-Stk1 were identified as putative regulatory targets of BA-Stp1. Further analysis found that T165 and S173 were necessary for optimal substrate phosphorylation, while S214 was necessary for complete ATP hydrolysis, autophosphorylation, and substrate phosphorylation. These findings provide insight into a previously undescribed Stp/Stk pair in B. anthracis.read more
Citations
More filters
Journal ArticleDOI
Eukaryote-Like Serine/Threonine Kinases and Phosphatases in Bacteria
TL;DR: Details into the enzymatic mechanism of eSTK activation derived from structural studies on both the ligand-binding and catalytic domains are discussed and the implications of these findings for understanding their physiological roles in these organisms are discussed.
Journal ArticleDOI
Protein Phosphatases of Pathogenic Bacteria: Role in Physiology and Virulence
TL;DR: The role of Ser/Thr- and Tyr-specific phosphatases present in pathogenic bacteria, with an emphasis on the regulation of basic cellular processes and virulence, are highlighted and the development of drugs targeting protein phosphatase targets are analyzed.
Journal ArticleDOI
Regulation of transcription by eukaryotic-like serine-threonine kinases and phosphatases in Gram-positive bacterial pathogens.
TL;DR: This work focuses on the ability of eSTKs and eSTPs in Gram-positive bacterial pathogens to directly modulate transcription, the known mechanistic outcomes of these modifications, and their roles as an added layer of complexity in controlling targeted RNA synthesis to enhance virulence potential.
Journal ArticleDOI
Hanks-Type Serine/Threonine Protein Kinases and Phosphatases in Bacteria: Roles in Signaling and Adaptation to Various Environments
TL;DR: The data show high complexity of bacterial regulatory network, in which the crosstalk between STK/STP signaling enzymes, components of TCSs, and the translational machinery occurs.
Journal ArticleDOI
In vitro Phosphorylation of Key Metabolic Enzymes from Bacillus subtilis: PrkC Phosphorylates Enzymes from Different Branches of Basic Metabolism
Nico Pietack,Dörte Becher,Sebastian R. Schmidl,Milton H. Saier,Michael Hecker,Fabian M. Commichau,Jörg Stülke +6 more
TL;DR: The agreement between in vivo and in vitro phosphorylation of HPr on Ser-12 suggests that the in vitro observations reflect the events that take place in the cell, and that PrkC is indeed able to phosphorylate several metabolic enzymes in vitro.
References
More filters
Journal ArticleDOI
A simple method of estimating fifty per cent endpoints
Lowell J. Reed,H. Muench +1 more
Journal ArticleDOI
Protein kinases and phosphatases: The Yin and Yang of protein phosphorylation and signaling
TL;DR: Although the use of PP inhibitors shows that there is significant basal PP activity in cells, it has become apparent that the activities of PPs are regulated in a sophisticated manner by a combination of targeting and regulatory subunits and by specific inhibitors.
Journal ArticleDOI
A systematic approach to the analysis of protein phosphorylation
TL;DR: The method is equally applicable to serine-, threonine- and tyrosine-phosphorylated proteins, and is capable of selectively isolating and identifying phosphopeptides present in a highly complex peptide mixture.
Journal ArticleDOI
Protein serine/threonine phosphatases: structure, regulation, and functions in cell growth
Marc C. Mumby,G. Walter +1 more
TL;DR: It is clear that much remains to be discovered regarding the roles of protein phosphatases in mitogenic signaling pathways, and the ability of okadaic acid to activate MAPK/ERKs demonstrates that alteration in serine/threonine dephosphorylation can have significant effects on common steps in growth stimulation induced by different types of mitogens.
Journal ArticleDOI
A eukaryotic-like Ser/Thr kinase signals bacteria to exit dormancy in response to peptidoglycan fragments
TL;DR: Staurosporine acts by blocking germination of dormant spores of dormant Bacillus subtilis spores by blocking muropeptide-dependent germination.