PathWhiz

PathWhiz ID	Pathway	Meta Data
PW123638 View Pathway	signaling sigH Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1) SigH is a key regulator of an extensive transcriptional network that responds to oxidative, nitrosative, and heat stresses in Mycobacterium tuberculosis, and this sigma factor is required for virulence in animal models of infection. SigH is negatively regulated by RshA, its cognate anti-sigma factor, which functions as a stress sensor and redox switch. While RshA provides a direct mechanism for sensing stress and activating transcription, bacteria use several types of signal transduction systems to sense the external environment. M. tuberculosis encodes several serine-threonine protein kinase signaling molecules, 2 of which, PknA and PknB, are essential and have been shown to regulate cell morphology and cell wall synthesis. In this work, we demonstrate that SigH and RshA are phosphorylated in vitro and in vivo by PknB. We show that phosphorylation of RshA, but not SigH, interferes with the interaction of these 2 proteins in vitro. Consistent with this finding, negative regulation of SigH activity by RshA in vivo is partially relieved in strains in which pknB is over-expressed, resulting in increased resistance to oxidative stress. These findings demonstrate an interaction between the signaling pathways mediated by PknB and the stress response regulon controlled by SigH. The intersection of these apparently discrete regulatory systems provides a mechanism by which limited activation of the SigH-dependent stress response in M. tuberculosis can be achieved. Coordination of the PknB and SigH regulatory pathways through phosphorylation of RshA may lead to adaptive responses that are important in the pathogenesis of M. tuberculosis infection. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Guest: Anonymous Created On: November 07, 2019 at 09:21 Last Updated: November 07, 2019 at 09:21
PW123640 View Pathway	signaling sigH Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) SigH is a key regulator of an extensive transcriptional network that responds to oxidative, nitrosative, and heat stresses in Mycobacterium tuberculosis, and this sigma factor is required for virulence in animal models of infection. SigH is negatively regulated by RshA, its cognate anti-sigma factor, which functions as a stress sensor and redox switch. While RshA provides a direct mechanism for sensing stress and activating transcription, bacteria use several types of signal transduction systems to sense the external environment. M. tuberculosis encodes several serine-threonine protein kinase signaling molecules, 2 of which, PknA and PknB, are essential and have been shown to regulate cell morphology and cell wall synthesis. In this work, we demonstrate that SigH and RshA are phosphorylated in vitro and in vivo by PknB. We show that phosphorylation of RshA, but not SigH, interferes with the interaction of these 2 proteins in vitro. Consistent with this finding, negative regulation of SigH activity by RshA in vivo is partially relieved in strains in which pknB is over-expressed, resulting in increased resistance to oxidative stress. These findings demonstrate an interaction between the signaling pathways mediated by PknB and the stress response regulon controlled by SigH. The intersection of these apparently discrete regulatory systems provides a mechanism by which limited activation of the SigH-dependent stress response in M. tuberculosis can be achieved. Coordination of the PknB and SigH regulatory pathways through phosphorylation of RshA may lead to adaptive responses that are important in the pathogenesis of M. tuberculosis infection. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Guest: Anonymous Created On: November 08, 2019 at 10:16 Last Updated: November 08, 2019 at 10:16
PW064707 View Pathway	signaling Sigma B Activation Bacteria BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Guest: Anonymous Created On: March 29, 2018 at 01:42 Last Updated: March 29, 2018 at 01:42
PW146361 View Pathway	drug action Silanol Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 18:01 Last Updated: October 07, 2023 at 18:01
PW126170 View Pathway	drug action Sildenafil Action Pathway Homo sapiens Sildenafil is a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction. Sexual stimulation causes the release of nitric oxide (NO) from nerves and endothelial cells into the penis. NO activates the enzyme guanylate cyclase.2 The activation of this enzyme is followed by the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP), activating a cascade of protein kinase-dependent phosphorylation events in smooth muscles, ultimately resulting in the dephosphorylation of myosin light chains within smooth muscle. This activity causes the relaxation of smooth muscle within blood vessels, resulting in the desired vasodilatory effect. Phosphodiesterase-5 breaks down cGMP to GMP. Sildenafil inhibits phosphodiesterase-5, preventing the breakdown of cGMP. This increases the concentration of cGMP, increasing the vasodilation and improving blood flow leading to penile erection. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Karxena Harford Created On: July 28, 2021 at 23:48 Last Updated: July 28, 2021 at 23:48
PW144334 View Pathway	drug action Sildenafil Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 13:25 Last Updated: October 07, 2023 at 13:25
PW175936 View Pathway	metabolic Sildenafil Predicted Metabolism Pathway Homo sapiens Sildenafil PIS1M1, Sildenafil PIS1M2, Sildenafil PIS2M1 are metabolites of Sildenafil predicted with biotransformer. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Omolola Created On: November 16, 2023 at 12:44 Last Updated: November 16, 2023 at 12:44
PW146253 View Pathway	drug action Silicon dioxide Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 17:47 Last Updated: October 07, 2023 at 17:47
PW146576 View Pathway	drug action Silicon Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 18:33 Last Updated: October 07, 2023 at 18:33
PW145677 View Pathway	drug action Silodosin Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 16:22 Last Updated: October 07, 2023 at 16:22