scholarly journals LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 241 ◽  
Author(s):  
Natalya Kraeva ◽  
Tereza Leštinová ◽  
Aygul Ishemgulova ◽  
Karolina Majerová ◽  
Anzhelika Butenko ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Bacterial Species ◽  
Signal Transduction Pathways ◽  
Leishmania Mexicana ◽  
Lipid Phosphatase ◽  
Dual Specificity ◽  
Primary Mouse ◽  
Human Infections ◽  
Specificity Protein

Protein phosphorylation/dephosphorylation is an important regulatory mechanism that controls many key physiological processes. Numerous pathogens successfully use kinases and phosphatases to internalize, replicate, and survive, modifying the host′s phosphorylation profile or signal transduction pathways. Multiple phosphatases and kinases from diverse bacterial pathogens have been implicated in human infections before. In this work, we have identified and characterized the dual specificity protein/lipid phosphatase LmDUSP1 as a novel virulence factor governing Leishmania mexicana infection. The LmDUSP1-encoding gene (LmxM.22.0250 in L. mexicana) has been acquired from bacteria via horizontal gene transfer. Importantly, its orthologues have been associated with virulence in several bacterial species, such as Mycobacterium tuberculosis and Listeria monocytogenes. Leishmania mexicana with ablated LmxM.22.0250 demonstrated severely attenuated virulence in the experimental infection of primary mouse macrophages, suggesting that this gene facilitates Leishmania pathogenicity in vertebrates. Despite significant upregulation of LmxM.22.0250 expression in metacyclic promastigotes, its ablation did not affect the ability of mutant cells to differentiate into virulent stages in insects. It remains to be further investigated which specific biochemical pathways involve LmDUSP1 and how this facilitates the parasite′s survival in the host. One of the interesting possibilities is that LmDUSP1 may target host′s substrate(s), thereby affecting its signal transduction pathways.

scholarly journals The dual-specificity CLK kinase induces neuronal differentiation of PC12 cells.

1994 ◽  
Vol 14 (10) ◽  
pp. 6954-6961 ◽  
Author(s):  
M P Myers ◽  
M B Murphy ◽  
G Landreth
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Protein Kinases ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Morphological Differentiation ◽  
Signal Transduction Pathways ◽  
Dual Specificity ◽  
Free Media ◽  
Specificity Protein

CLK is a dual-specificity protein kinase capable of phosphorylating serine, threonine, and tyrosine residues. We have investigated the action of CLK by establishing stable PC12 cell lines capable of inducibly expressing CLK. Expression of CLK in stably transfected PC12 cells mimicked a number of nerve growth factor (NGF)-dependent events, including the morphological differentiation of these cells and the elaboration of neurites. Moreover, CLK expression enhanced the rate of NGF-mediated neurite outgrowth of these cells, indicating that CLK expression and NGF treatment activate similar signal transduction pathways. CLK expression, unlike NGF, was not able to promote PC12 cell survival in serum-free media, demonstrating that CLK only partially recapitulated the actions of NGF on these cells and that the biochemical pathways necessary for morphological differentiation can be stimulated without also stimulating those necessary for survival. Induction of CLK expression also resulted in the selective activation of protein kinases that are components of growth factor-stimulated signal transduction cascades, including ERK1, ERK2, pp90RSK, and S6PKII. Induction of CLK expression, however, did not stimulate pp70S6K or Fos kinase, two NGF-sensitive protein kinases. These data indicate that CLK action mediates the morphological differentiation of these cells through its capacity to independently stimulate signal transduction pathways normally employed by NGF.

scholarly journals The dual-specificity CLK kinase induces neuronal differentiation of PC12 cells

1994 ◽  
Vol 14 (10) ◽  
pp. 6954-6961
Author(s):  
M P Myers ◽  
M B Murphy ◽  
G Landreth
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Protein Kinases ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Morphological Differentiation ◽  
Signal Transduction Pathways ◽  
Dual Specificity ◽  
Free Media ◽  
Specificity Protein

CLK is a dual-specificity protein kinase capable of phosphorylating serine, threonine, and tyrosine residues. We have investigated the action of CLK by establishing stable PC12 cell lines capable of inducibly expressing CLK. Expression of CLK in stably transfected PC12 cells mimicked a number of nerve growth factor (NGF)-dependent events, including the morphological differentiation of these cells and the elaboration of neurites. Moreover, CLK expression enhanced the rate of NGF-mediated neurite outgrowth of these cells, indicating that CLK expression and NGF treatment activate similar signal transduction pathways. CLK expression, unlike NGF, was not able to promote PC12 cell survival in serum-free media, demonstrating that CLK only partially recapitulated the actions of NGF on these cells and that the biochemical pathways necessary for morphological differentiation can be stimulated without also stimulating those necessary for survival. Induction of CLK expression also resulted in the selective activation of protein kinases that are components of growth factor-stimulated signal transduction cascades, including ERK1, ERK2, pp90RSK, and S6PKII. Induction of CLK expression, however, did not stimulate pp70S6K or Fos kinase, two NGF-sensitive protein kinases. These data indicate that CLK action mediates the morphological differentiation of these cells through its capacity to independently stimulate signal transduction pathways normally employed by NGF.

Oxoanions stimulate in vitro ovulation and signal transduction pathways in goldfish (Carassius auratus) follicles

1992 ◽  
Vol 263 (5) ◽  
pp. E943-E949 ◽  
Author(s):  
S. Y. Hsu ◽  
F. W. Goetz
Keyword(s):  
Signal Transduction ◽  
Carassius Auratus ◽  
Sodium Tungstate ◽  
Sodium Molybdate ◽  
Vanadyl Sulfate ◽  
Signal Transduction Pathways ◽  
Sodium Selenate ◽  
Sodium Chromate ◽  
Goldfish Carassius Auratus

The present study investigated the effects of a number of oxoanion compounds on in vitro ovulation of goldfish follicles and ovarian second messenger activities. Significant levels of ovulation were induced by 0.1 mM sodium chromate, 0.1 mM sodium metavanadate, 10 mM sodium molybdate, 0.1 mM sodium orthovanadate, 5 mM sodium selenate, 0.5 mM sodium tungstate, and 0.1 mM vanadyl sulfate. At levels that significantly stimulated ovulation, metavanadate, molybdate, orthovanadate, tungstate, and vanadyl sulfate also stimulated follicular phosphatidylinositol cycling and inhibited ovarian alkaline phosphatase activity. Moreover, the ovulation induced by these oxoanions was not inhibited by indomethacin (10 micrograms/ml), while ovulation induced by selenate and chromate was. In contrast, only vanadium-containing compounds significantly stimulated prostaglandin (PG) synthesis, and, in fact, selenate significantly inhibited PG production. Finally, only sodium molybdate- and vanadium-containing compounds appeared to increase follicular adenosine 3',5'-cyclic monophosphate content. While all oxoanions stimulated in vitro ovulation, they had differential effects on certain signal transduction pathways when tested at concentrations that stimulated in vitro ovulation. From the results, two basic groups could be delineated, one containing tungstate-, molybdate-, and vanadium-containing compounds and the other selenate and chromate. Thus the mechanism by which ovulation is induced by chromate and selenate may be different from that of vanadium-containing compounds, molybdate, and tungstate.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigating lipid signalling: it's all about finding the right PI

2008 ◽  
Vol 413 (1) ◽  
pp. e5-e6 ◽  
Author(s):  
Erik Nielsen
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Lipid Kinase ◽  
Phosphatase Activities ◽  
Cellular Signal Transduction ◽  
Lipid Signalling ◽  
Lipid Phosphatase ◽  
Biochemical Journal ◽  
Cellular Signal ◽  
The Right

Phosphoinositides are well-known components of cellular signal transduction pathways and, more recently, have been shown to play important roles in organelle identity and targeting determinants for various cytosolic proteins. Conversion of PtdIns into its various phosphorylated derivatives, such as PtdIns4P and PtdIns(4,5)P2, is accomplished by a series of distinct lipid kinase and lipid phosphatase activities that are localized to specific subcellular membranes. As a result, production of distinct PtdIns forms is thought to be largely dependent on the access of these enzymes to their PtdIns or PtdInsP substrates. Interestingly, an investigation of two different PIS (PtdIns synthase) isoforms by Lofke et al. in this issue of the Biochemical Journal now indicates that the ability of PtdIns to be converted into downstream PtdInsPs may depend upon the PIS isoform from which it was synthesized.

scholarly journals Redox Signal Transduction by the ArcB Sensor Kinase of Haemophilus influenzae Lacking the PAS Domain

2001 ◽  
Vol 183 (24) ◽  
pp. 7206-7212 ◽  
Author(s):  
Dimitris Georgellis ◽  
Ohsuk Kwon ◽  
Edmund C. C. Lin ◽  
Sandy M. Wong ◽  
Brian J. Akerley
Keyword(s):  
Signal Transduction ◽  
Haemophilus Influenzae ◽  
Bacterial Species ◽  
Redox Conditions ◽  
Sensor Kinase ◽  
Pas Domain ◽  
Signal Transduction System ◽  
E Coli ◽  
Two Component

ABSTRACT The Arc (anoxic redox control) two-component signal transduction system of Escherichia coli, which comprises the tripartite ArcB sensor kinase and the ArcA response regulator, modulates the expression of numerous operons in response to redox conditions of growth. We demonstrate that the arcA and arcBgenes of Haemophilus influenzae specify a two-component system. The Arc proteins of the two bacterial species sufficiently resemble each other that they can participate in heterologous transphosphorylation in vitro. Moreover, the Arc system of H. influenzae mediates transcriptional control according to the redox condition of growth both autologously in its own host and homologously in E. coli, indicating a high degree of functional conservation of the signal transduction system. The H. influenzae ArcB, however, lacks the PAS domain present in the region of E. coli ArcB linking the transmembrane to the cytosolic catalytic domains. Because the PAS domain participates in signal reception in a variety of sensory proteins, including sensors of molecular oxygen and redox state, a similar role was previously ascribed to it in ArcB. Our results demonstrate that the ArcB protein of H. influenzae mediates signal transduction in response to redox conditions of growth despite the absence of the PAS domain.

The PI3 kinase, p38 SAP kinase, and NF-κB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte–derived dendritic cells

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1039-1046 ◽  
Author(s):  
Kirit M. Ardeshna ◽  
Arnold R. Pizzey ◽  
Stephen Devereux ◽  
Asim Khwaja
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Human Monocyte ◽  
Functional Change ◽  
Pi3 Kinase ◽  
Signal Transduction Pathways ◽  
Hla Dr ◽  
Extracellular Signal ◽  
Induced Changes

Abstract As a dendritic cell (DC) matures, it becomes more potent as an antigen-presenting cell. This functional change is accompanied by a change in DC immunophenotype. The signal transduction events underlying this process are poorly characterized. In this study, we have investigated the signal transduction pathways involved in the lipopolysaccharide (LPS)-induced maturation of human monocyte–derived DCs (MoDCs) in vitro. We show that exposure of immature MoDCs to LPS activates the p38 stress-activated protein kinase (p38SAPK), extracellular signal–regulated protein kinase (ERK), phosphoinositide 3-OH kinase (PI3 kinase)/Akt, and nuclear factor (NF)-κB pathways. Studies using inhibitors demonstrate that PI3 kinase/Akt but not the other pathways are important in maintaining survival of LPS-stimulated MoDCs. Inhibiting p38SAPK prevented activation of the transcription factors ATF-2 and CREB and significantly reduced the LPS-induced up-regulation of CD80, CD83, and CD86, but did not have any significant effect on the LPS-induced changes in macropinocytosis or HLA-DR, CD40, and CD1a expression. Inhibiting the NF-κB pathway significantly reduced the LPS-induced up-regulation of HLA-DR as well as CD80, CD83, and CD86. Inhibiting the p38SAPK and NF-κB pathways simultaneously had variable effects depending on the cell surface marker studied. It thus appears that different aspects of LPS-induced MoDC maturation are regulated by different and sometimes overlapping pathways.

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