scholarly journals Role of Cell Surface Signaling in Proteolysis of an Alternative Sigma Factor in Pseudomonas aeruginosa

2008 ◽  
Vol 190 (14) ◽  
pp. 4865-4869 ◽  
Author(s):  
Matthew R. Spencer ◽  
Paul A. Beare ◽  
Iain L. Lamont
Keyword(s):  
Cell Surface ◽  
Signaling Pathway ◽  
Sigma Factor ◽  
Receptor Protein ◽  
Proteolytic Degradation ◽  
Alternative Sigma Factor ◽  
A Cell ◽  
Surface Signaling ◽  
Cell Surface Signaling ◽  
Antisigma Factor

ABSTRACT Alternative sigma factor proteins enable transcription of specific sets of genes in bacterial cells. Their activities can be controlled by posttranslational mechanisms including inhibition by antisigma proteins and proteolytic degradation. PvdS is an alternative sigma factor that is required for expression of genes involved in synthesis of a siderophore, pyoverdine, by Pseudomonas aeruginosa. In the absence of pyoverdine, the activity of PvdS is inhibited by a membrane-spanning antisigma factor, FpvR. Inhibition is relieved by a cell surface signaling pathway. In this pathway, a combination of pyoverdine and a cell surface receptor protein, FpvA, suppresses the antisigma activity of FpvR, enabling transcription of PvdS-dependent genes. In this research, we investigated proteolytic degradation of PvdS in response to the signaling pathway. Proteolysis of PvdS was observed in strains of P. aeruginosa in which FpvR had anti-sigma factor activity due to the absence of pyoverdine or the FpvA receptor protein or overproduction of FpvR. Suppression of antisigma activity by addition of pyoverdine or through the absence of FpvR prevented detectable proteolysis of PvdS. The amounts of PvdS were less in bacteria in which proteolysis was observed, and reporter gene assays showed that this reduction was not due to decreased expression of PvdS. In wild-type bacteria, there was an average of 730 molecules of PvdS per cell in late exponential growth phase. Our results show that proteolysis and amounts of PvdS are affected by the antisigma factor FpvR and that this activity of FpvR is controlled by the cell surface signaling pathway.

scholarly journals CCR5 is a required signaling receptor for macrophage expression of inflammatory genes in response to viral double-stranded RNA

2019 ◽  
Vol 316 (5) ◽  
pp. R525-R534 ◽  
Author(s):  
Zachary R. Shaheen ◽  
Benjamin S. Christmann ◽  
Joshua D. Stafford ◽  
Jason M. Moran ◽  
R. Mark L. Buller ◽  
...  
Keyword(s):  
Cell Surface ◽  
Poly I:C ◽  
Viral Dsrna ◽  
Inflammatory Genes ◽  
Chemokine Ligand ◽  
A Cell ◽  
Surface Signaling ◽  
Cell Surface Signaling ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Double-stranded (ds) RNA, both synthetic and produced during virus replication, rapidly stimulates MAPK and NF-κB signaling that results in expression of the inflammatory genes inducible nitric oxide synthase, cyclooxygenase 2, and IL-1β by macrophages. Using biochemical and genetic approaches, we have identified the chemokine ligand-binding C-C chemokine receptor type 5 (CCR5) as a cell surface signaling receptor required for macrophage expression of inflammatory genes in response to dsRNA. Activation of macrophages by synthetic dsRNA does not require known dsRNA receptors, as poly(inosinic:cytidylic) acid [poly(I:C)] activates signaling pathways leading to expression of inflammatory genes to similar levels in wild-type and Toll-like receptor 3- or melanoma differentiation antigen 5-deficient macrophages. In contrast, macrophage activation in response to poly(I:C) is attenuated in macrophages isolated from mice lacking CCR5. These findings support a role for CCR5 as a cell surface signaling receptor that participates in activation of inflammatory genes in macrophages in response to the viral dsRNA mimetic poly(inosinic:cytidylic) acid by pathways that are distinct from classical dsRNA receptor-mediated responses.

The Presence of Anti-GRP78 Antibodies in the Serum of Patients with Colorectal Carcinoma: A Potential Biomarker for Early Cancer Detection

2014 ◽  
Vol 29 (4) ◽  
pp. 431-435 ◽  
Author(s):  
Annat Raiter ◽  
Alexander Vilkin ◽  
Rachel Gingold ◽  
Zohar Levi ◽  
Marisa Halpern ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cell Surface ◽  
Physiological Stress ◽  
Igg Antibody ◽  
Potential Biomarker ◽  
Protein Functions ◽  
A Cell ◽  
Surface Signaling ◽  
Cell Surface Signaling ◽  
New Biomarkers

Background The identification of new biomarkers is required for early diagnosis of colorectal carcinoma patients (CRC), since about 20% of these patients are initially diagnosed with a distant metastatic disease. GRP78, a heat shock protein, functions also as a cell surface signaling receptor of cells under physiological stress. GRP78 was found to be expressed on the cell surface of various tumor cells. The presence of autoantibodies to GRP78 in cancer patient's serum was found to be correlated with a poor prognosis. In this study we aimed to identify anti-GRP78 antibodies in the serum of 85 patients diagnosed by colonoscopy, as an early detection biomarker. Methods We developed an ELISA assay with recombinant GRP78 immobilized on 96-well culture plates and used an anti-IgG antibody to measure the sole anti-GRP78 IgGs. Results Testing for anti-GRP78 showed a significant increase in antibody titer in patients with a polyp and in CRC patients (p<0.001) compared to healthy subjects. Conclusions This is the first study showing the presence of anti-GRP78 at the very early stages of CRC.

scholarly journals Identification of Proteins Associating with Glycosylphosphatidylinositol- Anchored T-Cadherin on the Surface of Vascular Endothelial Cells: Role for Grp78/BiP in T-Cadherin-Dependent Cell Survival

2008 ◽  
Vol 28 (12) ◽  
pp. 4004-4017 ◽  
Author(s):  
Maria Philippova ◽  
Danila Ivanov ◽  
Manjunath B. Joshi ◽  
Emmanouil Kyriakakis ◽  
Katharina Rupp ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Cell Survival ◽  
High Performance ◽  
Vascular Endothelial Cells ◽  
Surface Lipid ◽  
Gaba A ◽  
Dependent Cell ◽  
A Cell ◽  
Cell Surface Signaling

ABSTRACT There is scant knowledge regarding how cell surface lipid-anchored T-cadherin (T-cad) transmits signals through the plasma membrane to its intracellular targets. This study aimed to identify membrane proteins colocalizing with atypical glycosylphosphatidylinositol (GPI)-anchored T-cad on the surface of endothelial cells and to evaluate their role as signaling adaptors for T-cad. Application of coimmunoprecipitation from endothelial cells expressing c-myc-tagged T-cad and high-performance liquid chromatography revealed putative association of T-cad with the following proteins: glucose-related protein GRP78, GABA-A receptor α1 subunit, integrin β3, and two hypothetical proteins, LOC124245 and FLJ32070. Association of Grp78 and integrin β3 with T-cad on the cell surface was confirmed by surface biotinylation and reciprocal immunoprecipitation and by confocal microscopy. Use of anti-Grp78 blocking antibodies, Grp78 small interfering RNA, and coexpression of constitutively active Akt demonstrated an essential role for surface Grp78 in T-cad-dependent survival signal transduction via Akt in endothelial cells. The findings herein are relevant in the context of both the identification of transmembrane signaling partners for GPI-anchored T-cad as well as the demonstration of a novel mechanism whereby Grp78 can influence endothelial cell survival as a cell surface signaling receptor rather than an intracellular chaperone.

scholarly journals Control of Acid Resistance inEscherichia coli

1999 ◽  
Vol 181 (11) ◽  
pp. 3525-3535 ◽  
Author(s):  
Marie-Pierre Castanie-Cornet ◽  
Thomas A. Penfound ◽  
Dean Smith ◽  
John F. Elliott ◽  
John W. Foster
Keyword(s):  
Stationary Phase ◽  
Sigma Factor ◽  
Glutamate Decarboxylase ◽  
Glucose Repression ◽  
Acid Resistance ◽  
Receptor Protein ◽  
Phase Cell ◽  
Alternative Sigma Factor ◽  
E Coli ◽  
Acid Challenge

ABSTRACT Acid resistance (AR) in Escherichia coli is defined as the ability to withstand an acid challenge of pH 2.5 or less and is a trait generally restricted to stationary-phase cells. Earlier reports described three AR systems in E. coli. In the present study, the genetics and control of these three systems have been more clearly defined. Expression of the first AR system (designated the oxidative or glucose-repressed AR system) was previously shown to require the alternative sigma factor RpoS. Consistent with glucose repression, this system also proved to be dependent in many situations on the cyclic AMP receptor protein. The second AR system required the addition of arginine during pH 2.5 acid challenge, the structural gene for arginine decarboxylase (adiA), and the regulatorcysB, confirming earlier reports. The third AR system required glutamate for protection at pH 2.5, one of two genes encoding glutamate decarboxylase (gadA or gadB), and the gene encoding the putative glutamate:γ-aminobutyric acid antiporter (gadC). Only one of the two glutamate decarboxylases was needed for protection at pH 2.5. However, survival at pH 2 required both glutamate decarboxylase isozymes. Stationary phase and acid pH regulation of the gad genes proved separable. Stationary-phase induction of gadA and gadBrequired the alternative sigma factor ςS encoded byrpoS. However, acid induction of these enzymes, which was demonstrated to occur in exponential- and stationary-phase cells, proved to be ςS independent. Neither gad gene required the presence of volatile fatty acids for induction. The data also indicate that AR via the amino acid decarboxylase systems requires more than an inducible decarboxylase and antiporter. Another surprising finding was that the ςS-dependent oxidative system, originally thought to be acid induced, actually proved to be induced following entry into stationary phase regardless of the pH. However, an inhibitor produced at pH 8 somehow interferes with the activity of this system, giving the illusion of acid induction. The results also revealed that the AR system affording the most effective protection at pH 2 in complex medium (either Luria-Bertani broth or brain heart infusion broth plus 0.4% glucose) is the glutamate-dependent GAD system. Thus, E. coli possesses three overlapping acid survival systems whose various levels of control and differing requirements for activity ensure that at least one system will be available to protect the stationary-phase cell under naturally occurring acidic environments.

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