scholarly journals LrrkA, a kinase with leucine‐rich repeats, links folate sensing with Kil2 activity and intracellular killing

2019 ◽  
Vol 22 (1) ◽  
Author(s):  
Romain Bodinier ◽  
Jade Leiba ◽  
Ayman Sabra ◽  
Tania N. Jauslin ◽  
Otmane Lamrabet ◽  
...  
Keyword(s):  
Intracellular Killing ◽  
Leucine Rich Repeats

scholarly journals Nucleotide-Binding Leucine-Rich Repeat Genes CsRSF1 and CsRSF2 Are Positive Modulators in the Cucumis sativus Defense Response to Sphaerotheca fuliginea

2021 ◽  
Vol 22 (8) ◽  
pp. 3986
Author(s):  
Xue Wang ◽  
Qiumin Chen ◽  
Jingnan Huang ◽  
Xiangnan Meng ◽  
Na Cui ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Defense Response ◽  
Nucleotide Binding ◽  
Plant Defense Response ◽  
Sphaerotheca Fuliginea ◽  
Leucine Rich Repeat ◽  
Transcript Levels ◽  
Yield And Quality ◽  
Leucine Rich Repeats ◽  
Exogenous Substances

Cucumber powdery mildew caused by Sphaerotheca fuliginea is a leaf disease that seriously affects cucumber’s yield and quality. This study aimed to report two nucleotide-binding site-leucine-rich repeats (NBS-LRR) genes CsRSF1 and CsRSF2, which participated in regulating the resistance of cucumber to S. fuliginea. The subcellular localization showed that the CsRSF1 protein was localized in the nucleus, cytoplasm, and cell membrane, while the CsRSF2 protein was localized in the cell membrane and cytoplasm. In addition, the transcript levels of CsRSF1 and CsRSF2 were different between resistant and susceptible cultivars after treatment with exogenous substances, such as abscisic acid (ABA), methyl jasmonate (MeJA), salicylic acid (SA), ethephon (ETH), gibberellin (GA) and hydrogen peroxide (H2O2). The expression analysis showed that the transcript levels of CsRSF1 and CsRSF2 were correlated with plant defense response against S. fuliginea. Moreover, the silencing of CsRSF1 and CsRSF2 impaired host resistance to S. fuliginea, but CsRSF1 and CsRSF2 overexpression improved resistance to S. fuliginea in cucumber. These results showed that CsRSF1 and CsRSF2 genes positively contributed to the resistance of cucumber to S. fuliginea. At the same time, CsRSF1 and CsRSF2 genes could also regulate the expression of defense-related genes. The findings of this study might help enhance the resistance of cucumber to S. fuliginea.

scholarly journals LRIG1 is a conserved EGFR regulator involved in melanoma development, survival and treatment resistance

Oncogene ◽  
2021 ◽  
Author(s):  
Ola Billing ◽  
Ylva Holmgren ◽  
Daniel Nosek ◽  
Håkan Hedman ◽  
Oskar Hemmingsson
Keyword(s):  
Growth Factor Receptor ◽  
Braf Inhibitor ◽  
Treatment Resistance ◽  
Negative Regulator ◽  
C Elegans ◽  
Rtk Signaling ◽  
Egfr Expression ◽  
Inhibitor Resistance ◽  
Leucine Rich Repeats

AbstractLeucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a pan-negative regulator of receptor tyrosine kinase (RTK) signaling and a tumor suppressor in several cancers, but its involvement in melanoma is largely unexplored. Here, we aim to determine the role of LRIG1 in melanoma tumorigenesis, RTK signaling, and BRAF inhibitor resistance. We find that LRIG1 is downregulated during early tumorigenesis and that LRIG1 affects activation of the epidermal growth factor receptor (EGFR) in melanoma cells. LRIG1-dependent regulation of EGFR signaling is evolutionary conserved to the roundworm C. elegans, where negative regulation of the EGFR-Ras-Raf pathway by sma-10/LRIG completely depends on presence of the receptor let-23/EGFR. In a cohort of metastatic melanoma patients, we observe an association between LRIG1 and survival in the triple wild-type subtype and in tumors with high EGFR expression. During in vitro development of BRAF inhibitor resistance, LRIG1 expression decreases; and mimics LRIG1 knockout cells for increased EGFR expression. Treating resistant cells with recombinant LRIG1 suppresses AKT activation and proliferation. Together, our results show that sma-10/LRIG is a conserved regulator of RTK signaling, add to our understanding of LRIG1 in melanoma and identifies recombinant LRIG1 as a potential therapeutic against BRAF inhibitor-resistant melanoma.

Defective intracellular killing of micro-organisms by murine alveolar macrophages

1989 ◽  
Vol 26 (1-2) ◽  
pp. 206-207 ◽  
Author(s):  
P. H. Nibbering ◽  
M. T. Barselaar ◽  
J. S. Gevel ◽  
R. Furth
Keyword(s):  
Alveolar Macrophages ◽  
Intracellular Killing ◽  
Micro Organisms

Intracellular killing of Trichophyton mentagrophytes microconidia by normal human polymorphonuclear leukocytes

1985 ◽  
Vol 278 (1) ◽  
pp. 77-78 ◽  
Author(s):  
H. Hauck ◽  
M. Skořepová ◽  
M. Simon ◽  
D. Djawari
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Trichophyton Mentagrophytes ◽  
Intracellular Killing ◽  
Normal Human ◽  
Human Polymorphonuclear Leukocytes

scholarly journals Gamma Interferon Enhances Internalization and Early Nonoxidative Killing of Salmonella enterica Serovar Typhimurium by Human Macrophages and Modifies Cytokine Responses

2005 ◽  
Vol 73 (6) ◽  
pp. 3445-3452 ◽  
Author(s):  
Melita A. Gordon ◽  
Dominic L. Jack ◽  
David H. Dockrell ◽  
Margaret E. Lee ◽  
Robert C. Read
Keyword(s):  
Oxidative Burst ◽  
Respiratory Burst ◽  
Salmonella Enterica ◽  
Gamma Interferon ◽  
Cytokine Release ◽  
Intracellular Killing ◽  
Human Macrophages ◽  
Salmonella Infections ◽  
Serovar Typhimurium ◽  
Ifn Γ

ABSTRACT Gamma interferon (IFN-γ) is a critical cytokine in host defense against salmonella infections, but its role in phagocytic killing of intracellular Salmonella spp. has been investigated mainly in animal rather than human cells. We measured the effect of recombinant IFN-γ (rIFN-γ) priming on bacterial internalization, intracellular killing, oxidative burst, and cytokine release during phagocytosis of Salmonella enterica serovar Typhimurium by human monocyte-derived macrophages (MDM). Eleven-day-old MDM, primed for 72 h with rIFN-γ (100 ng/ml) exhibited an increased proportion of cells with associated bacteria (31% versus 26%, P = 0.036) and a 67% increase in internalized bacteria per cell compared to unprimed cells (P = 0.025). Retrieval of viable bacteria following internalization was reduced 3.6-fold in 72-h primed versus unprimed MDM (interquartile range, 3.1 to 6.4) at 0.5 h due to enhanced early intracellular killing, and this difference was maintained up to 24 h. In contrast, cells primed for only 24 h exhibited no increase in early killing. MDM were competent to produce an early oxidative burst when stimulated with phorbol myristate acetate, which was fully abrogated by the respiratory burst inhibitor diphenyleneiodonium chloride (DPI), but infection of MDM with S. enterica serovar Typhimurium did not cause an increase in the early respiratory burst under unprimed or primed conditions, and DPI had no effect on the early killing of bacteria by primed or unprimed MDM. During 24 h following infection, rIFN-γ-primed MDM released more interleukin-12 (IL-12) and less IL-10 relative to unprimed cells. We conclude that 72-h priming with rIFN-γ increases the efficiency of internalization and nonoxidative early intracellular killing of S. enterica serovar Typhimurium by human macrophages and modifies subsequent cytokine release.

Corticosteroids in the Management of Cystitis Secondary to Chronic Granulomatous Disease

PEDIATRICS ◽  
1990 ◽  
Vol 85 (2) ◽  
pp. 219-221
Author(s):  
REBECCA J. COLLMAN ◽  
JOSEPH D. DICKERMAN
Keyword(s):  
Chronic Granulomatous Disease ◽  
Oxidative Metabolism ◽  
Phagocytic Cell ◽  
Granulomatous Disease ◽  
Intracellular Killing ◽  
Inherited Disorders ◽  
Recurrent Pyogenic Infections

Chronic granulomatous disease refers to a group of inherited disorders characterized by a deficit in phagocytic-cell oxidative metabolism, resulting in recurrent pyogenic infections due to defective intracellular killing of microorganisms.1 Granulomas form in various organs or tissues, presumably in an attempt to "wall off" the infection, and these can be a major cause of morbidity when vital structures are obstructed or compromised. Cultures of the granulomas are usually negative, although antibiotics have been advocated in the treatment of this complication. Recently, three patients with chronic granulomatous disease-two with gastrointestinal and genitourinary involvement2 and one with pulmonary involvement3—were treated with corticosteroids, which resulted in an amelioration of symptoms.

Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)–deficient mice

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 689-697 ◽  
Author(s):  
Roman Dziarski ◽  
Kenneth A. Platt ◽  
Eva Gelius ◽  
Håkan Steiner ◽  
Dipika Gupta
Keyword(s):  
Inflammatory Responses ◽  
Protein S ◽  
Intracellular Killing ◽  
Gram Positive ◽  
Peptidoglycan Recognition Protein ◽  
Susceptibility To Infection ◽  
Gram Positive Bacteria ◽  
Recognition Protein ◽  
Factor Α ◽  
Increased Susceptibility

AbstractInsect peptidoglycan recognition protein-S (PGRP-S), a member of a family of innate immunity pattern recognition molecules conserved from insects to mammals, recognizes bacterial cell wall peptidoglycan and activates 2 antimicrobial defense systems, prophenoloxidase cascade and antimicrobial peptides through Toll receptor. We show that mouse PGRP-S is present in neutrophil tertiary granules and that PGRP-S–deficient (PGRP-S-/-) mice have increased susceptibility to intraperitoneal infection with gram-positive bacteria of low pathogenicity but not with more pathogenic gram-positive or gram-negative bacteria. PGRP-S-/- mice have normal inflammatory responses and production of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Neutrophils from PGRP-S-/- mice have normal phagocytic uptake of bacteria but are defective in intracellular killing and digestion of relatively nonpathogenic gram-positive bacteria. Therefore, mammalian PGRP-S functions in intracellular killing of bacteria. Thus, only bacterial recognition by PGRP-S, but not its effector function, is conserved from insects to mammals.

scholarly journals Conserved charged residues in the leucine-rich repeat domain of the Ran GTPase activating protein are required for Ran binding and GTPase activation

1999 ◽  
Vol 343 (3) ◽  
pp. 653-662 ◽  
Author(s):  
Jörg HABERLAND ◽  
Volker GERKE
Keyword(s):  
Nucleocytoplasmic Transport ◽  
Small Gtpases ◽  
Structural Basis ◽  
Ran Gtpase ◽  
Protein Protein Interaction ◽  
Charged Residues ◽  
Gtpase Activation ◽  
Gtpase Cycle ◽  
Leucine Rich Repeats ◽  
Lrr Domain

GTPase activating proteins (GAPs) for Ran, a Ras-related GTPase participating in nucleocytoplasmic transport, have been identified in different species ranging from yeast to man. All RanGAPs are characterized by a conserved domain consisting of eight leucine-rich repeats (LRRs) interrupted at two positions by so-called separating regions, the latter being unique for RanGAPs within the family of LRR proteins. The cytosolic RanGAP activity is essential for the Ran GTPase cycle which in turn provides directionality in nucleocytoplasmic transport, but the structural basis for the interaction between Ran and its GAP has not been elucidated. In order to gain a better understanding of this interaction we generated a number of mutant RanGAPs carrying amino acid substitutions in the LRR domain and analysed their complex formation with Ran as well as their ability to stimulate the intrinsic GTPase activity of the G protein. We show that conserved charged residues present in the separating regions of the LRR domain are indispensable for efficient Ran binding and GAP activity. These separating regions contain three conserved arginines which could possibly serve as catalytic residues similar to the arginine fingers identified in GAPs for other small GTPases. However, mutations in two of these arginines do not affect the GAP activity and replacement of the third conserved arginine (Arg91 in human RanGAP) severely interferes not only with GAP activity but also with Ran binding. This indicates that RanGAP-stimulated GTP hydrolysis on Ran does not involve a catalytic arginine residue but requires certain charged residues of the LRR domain of the GAP for mediating the protein-protein interaction.

scholarly journals TAP (NXF1) Belongs to a Multigene Family of Putative RNA Export Factors with a Conserved Modular Architecture

2000 ◽  
Vol 20 (23) ◽  
pp. 8996-9008 ◽  
Author(s):  
Andrea Herold ◽  
Mikita Suyama ◽  
João P. Rodrigues ◽  
Isabelle C. Braun ◽  
Ulrike Kutay ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Rna Binding ◽  
Mrna Export ◽  
Modular Architecture ◽  
Export Activity ◽  
Evolutionarily Conserved ◽  
Rna Export ◽  
Higher Eukaryotes ◽  
Leucine Rich Repeats ◽  
Rna Export Factors

ABSTRACT Vertebrate TAP (also called NXF1) and its yeast orthologue, Mex67p, have been implicated in the export of mRNAs from the nucleus. The TAP protein includes a noncanonical RNP-type RNA binding domain, four leucine-rich repeats, an NTF2-like domain that allows heterodimerization with p15 (also called NXT1), and a ubiquitin-associated domain that mediates the interaction with nucleoporins. Here we show that TAP belongs to an evolutionarily conserved family of proteins that has more than one member in higher eukaryotes. Not only the overall domain organization but also residues important for p15 and nucleoporin interaction are conserved in most family members. We characterize two of four human TAP homologues and show that one of them, NXF2, binds RNA, localizes to the nuclear envelope, and exhibits RNA export activity. NXF3, which does not bind RNA or localize to the nuclear rim, has no RNA export activity. Database searches revealed that although only one p15(nxt) gene is present in the Drosophila melanogaster and Caenorhabditis elegans genomes, there is at least one additional p15 homologue (p15-2 [also called NXT2]) encoded by the human genome. Both human p15 homologues bind TAP, NXF2, and NXF3. Together, our results indicate that the TAP-p15 mRNA export pathway has diversified in higher eukaryotes compared to yeast, perhaps reflecting a greater substrate complexity.

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