Severe combined immune deficiencies due to defects of the common ? chain-JAK3 signaling pathway

1998 ◽  
Vol 19 (4) ◽  
pp. 401-415 ◽  
Author(s):  
Fabio Candotti ◽  
John J. O'Shea ◽  
Anna Villa
Keyword(s):  
Signaling Pathway ◽  
Immune Deficiencies ◽  
The Common

scholarly journals The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1188
Author(s):  
Jian Yi Chai ◽  
Vaisnevee Sugumar ◽  
Mohammed Abdullah Alshawsh ◽  
Won Fen Wong ◽  
Aditya Arya ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Clinical Settings ◽  
Developmental Studies ◽  
Holistic View ◽  
Gli Transcription Factors ◽  
Cancer Initiation ◽  
The Common

The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved among mammals, with crucial roles in regulating embryonic development as well as in cancer initiation and progression. The GLI transcription factors (GLI1, GLI2, and GLI3) are effectors of the Hh pathway and are regulated via Smoothened (SMO)-dependent and SMO-independent mechanisms. The SMO-dependent route involves the common Hh-PTCH-SMO axis, and mutations or transcriptional and epigenetic dysregulation at these levels lead to the constitutive activation of GLI transcription factors. Conversely, the SMO-independent route involves the SMO bypass regulation of GLI transcription factors by external signaling pathways and their interacting proteins or by epigenetic and transcriptional regulation of GLI transcription factors expression. Both routes of GLI activation, when dysregulated, have been heavily implicated in tumorigenesis of many known cancers, making them important targets for cancer treatment. Hence, this review describes the various SMO-dependent and SMO-independent routes of GLI regulation in the tumorigenesis of multiple cancers in order to provide a holistic view of the paradigms of hedgehog signaling networks involving GLI regulation. An in-depth understanding of the complex interplay between GLI and various signaling elements could help inspire new therapeutic breakthroughs for the treatment of Hh-GLI-dependent cancers in the future. Lastly, we have presented an up-to-date summary of the latest findings concerning the use of Hh inhibitors in clinical developmental studies and discussed the challenges, perspectives, and possible directions regarding the use of SMO/GLI inhibitors in clinical settings.

The common symbiotic signaling pathway ( CSSP or SYM )

2019 ◽  
pp. 521-521
Author(s):  
Frans J. Bruijn
Keyword(s):  
Signaling Pathway ◽  
The Common

scholarly journals Construction of an miRNA-Regulated Pathway Network Reveals Candidate Biomarkers for Postmenopausal Osteoporosis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Min Shao
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Akt Signaling Pathway ◽  
Pathway Network ◽  
Context Score ◽  
The Common ◽  
The Individual

We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP) via establishing an microRNAs- (miRNA-) regulated pathway network (MRPN). Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS). Significant pathways based on differentially expressed genes (DEGs) using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods. Next, miRNAs prediction was implemented via calculating TargetScore values with precomputed input (log fold change (FC), TargetScan context score (TSCS), and probabilities of conserved targeting (PCT)). An MRPN construction was constructed using the common genes in the common pathways and the predicted miRNAs. Using false discovery rate (FDR) < 0.05, 279 differential pathways were identified. Using the criteria of FDR < 0.05 and log⁡FC≥2, 39 DEGs were retrieved, and these DEGs were enriched in 64 significant pathways identified by DAVID. Overall, 27 pathways were the common ones between two methods. Importantly, MAPK signaling pathway and PI3K-Akt signaling pathway were the first and second significantly enriched ones, respectively. These 27 common pathways separated PMOP from controls with the accuracy of 0.912. MAPK signaling pathway and PI3K/Akt signaling pathway might play crucial roles in PMOP.

scholarly journals Computational Biophysical, Biochemical, and Evolutionary Signature of Human R-Spondin Family Proteins, the Member of Canonical Wnt/β-Catenin Signaling Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Ashish Ranjan Sharma ◽  
Chiranjib Chakraborty ◽  
Sang-Soo Lee ◽  
Garima Sharma ◽  
Jeong Kyo Yoon ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Computational Algorithm ◽  
Biophysical Properties ◽  
Glycosylation Sites ◽  
Peptide Length ◽  
Basic Understanding ◽  
Therapeutic Properties ◽  
The Common ◽  
Canonical Wnt ◽  
Positively Charged

In human, Wnt/β-catenin signaling pathway plays a significant role in cell growth, cell development, and disease pathogenesis. Four human (Rspo)s are known to activate canonical Wnt/β-catenin signaling pathway. Presently, (Rspo)s serve as therapeutic target for several human diseases. Henceforth, basic understanding about the molecular properties of (Rspo)s is essential. We approached this issue by interpreting the biochemical and biophysical properties along with molecular evolution of (Rspo)s thorough computational algorithm methods. Our analysis shows that signal peptide length is roughly similar in (Rspo)s family along with similarity in aa distribution pattern. In Rspo3, four N-glycosylation sites were noted. All members are hydrophilic in nature and showed alike GRAVY values, approximately. Conversely, Rspo3 contains the maximum positively charged residues while Rspo4 includes the lowest. Four highly aligned blocks were recorded through Gblocks. Phylogenetic analysis shows Rspo4 is being rooted with Rspo2 and similarly Rspo3 and Rspo1 have the common point of origin. Through phylogenomics study, we developed a phylogenetic tree of sixty proteins (n=60) with the orthologs and paralogs seed sequences. Protein-protein network was also illustrated. Results demonstrated in our study may help the future researchers to unfold significant physiological and therapeutic properties of (Rspo)s in various disease models.

scholarly journals Rice responds to endophytic colonization which is independent of the common symbiotic signaling pathway

2015 ◽  
Vol 208 (2) ◽  
pp. 531-543 ◽  
Author(s):  
Xi Chen ◽  
Lucie Miché ◽  
Sabrina Sachs ◽  
Qi Wang ◽  
Anna Buschart ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Endophytic Colonization ◽  
The Common

scholarly journals Comprehensive Transcriptomic Comparison between Porcine CD8− and CD8+ Gamma Delta T Cells Revealed Distinct Immune Phenotype

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2165
Author(s):  
Sangwook Kim ◽  
Byeonghwi Lim ◽  
Sameer-ul-Salam Mattoo ◽  
Eun-Young Oh ◽  
Chang-Gi Jeong ◽  
...  
Keyword(s):  
T Cells ◽  
Signaling Pathway ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
Sequencing Analysis ◽  
Gamma Delta ◽  
Tcr Signaling ◽  
The Common

We aimed to comprehensively understand the functional mechanisms of immunity, especially of the CD8+/− subsets of gamma delta (γδ) T cells, using an RNA-sequencing analysis. Herein, γδ T cells were obtained from bronchial lymph node tissues of 38-day-old (after weaning 10-day: D10) and 56-day-old (after weaning 28-day: D28) weaned pigs and sorted into CD8+ and CD8− groups. Differentially expressed genes (DEGs) were identified based on the CD8 groups at D10 and D28 time points. We confirmed 1699 DEGs between D10 CD8+ versus D10 CD8− groups and 1784 DEGs between D28 CD8+ versus D28 CD8− groups; 646 upregulated and 561 downregulated DEGs were common. The common upregulated DEGs were enriched in the cytokine–cytokine receptor interaction and T cell receptor (TCR) signaling pathway, and the common downregulated DEGs were enriched in the B cell receptor signaling pathway. Further, chemokine-related genes, interferon gamma, and CD40 ligand were involved in the cytokine–cytokine receptor interaction and TCR signaling pathway, which are associated with inter-regulation in immunity. We expect our results to form the basic data required for understanding the mechanisms of γδ T cells in pigs; however, further studies are required in order to reveal the dynamic changes in γδ T cells under pathogenic infections, such as those by viruses.

scholarly journals Major components in the KARRIKIN INSENSITIVE2-ligand signaling pathway are conserved in the liverwort, Marchantia polymorpha

2020 ◽  
Author(s):  
Yohei Mizuno ◽  
Aino Komatsu ◽  
Shota Shimazaki ◽  
Xiaonan Xie ◽  
Kimitsune Ishizaki ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ubiquitin Ligase ◽  
Common Ancestor ◽  
Marchantia Polymorpha ◽  
Wild Type ◽  
Knock Out ◽  
Ubiquitin Ligase Complex ◽  
The Common ◽  
F Box Protein ◽  
And Control

AbstractKARRIKIN INSENSITIVE2 (KAI2) was first identified in Arabidopsis thaliana as a receptor of karrikin, a smoke-derived germination stimulant. KAI2 is also considered a receptor of an unidentified endogenous molecule called the KAI2-ligand (KL). Upon KAI2 activation, signals are transmitted through degradation of D53/SMXL proteins via ubiquitination by a Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. All components in the KL signaling pathway exist in the liverwort Marchantia polymorpha, namely MpKAI2A and MpKAI2B, MpMAX2 encoding the F-box protein, and MpSMXL, indicating that the signaling pathway became functional in the common ancestor of bryophytes and seed plants. Genetic analysis using knock-out mutants of these KL signaling genes, produced using the CRISPR system, indicated that MpKAI2A, MpMAX2 and MpSMXL act in the same genetic pathway and control early gemma growth. Introduction of MpSMXLd53, in which a domain required for degradation is mutated, into wild-type plants caused phenotypes resembling those of the Mpkai2a and Mpmax2 mutants. In addition, Citrine fluorescence was detected in tobacco cells transiently transformed with the 35S:MpSMXL-Citrine gene construct and treated with MG132, a proteasome inhibitor. On the other hand, introduction of 35S:MpSMXLd53-Citrine conferred Citrine fluorescence without MG132 treatment. These findings imply that MpSMXL is subjected to degradation, and that degradation of MpSMXL is crucial for KL signaling in M. polymorpha. We also showed that MpSMXL is negatively regulated by KL signaling. Taken together, this study demonstrates that basic mechanisms in the KL signaling pathway are conserved in M. polymorpha.

Network Pharmacology Analysis of Molecular Mechanism of Curcuma Longa L. extracts Regulating Glioma Immune Inflammatory Factors: Implications for Precise Cancer Treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Hui Li ◽  
Yongwei Li
Keyword(s):  
Cell Differentiation ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Curcuma Longa ◽  
Interleukin 4 ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Regulatory Pathway ◽  
Active Components ◽  
The Common

Introduction: : Curcuma longa L. has been associated with different antioxidant, anti-inflammatory, bactericidal and anticancer effects, but the mechanisms of the effects are not yet clearly understood. This study aimed to investigate the key targets and the effect of potential molecular mechanisms of Curcuma longa L. extracts on glioma using different network pharmacology analysis approaches. Methods: The components of Curcuma longa were extracted by gas chromatography-mass spectrometry (GC-MS), and the active components related to the occurrence and development of glioma were determined by traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database, and the same targets of the active components and glioma were screened by network pharmacology approach. Then, the protein’s function and regulatory pathway of the common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The protein’s action and regulatory pathway of the common targets were analyzed with the Cytoscape package using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to construct the target interaction network through which the key targets were identified. Results : GC-MS combined with TCMSP database was used to identify the active components related to the occurrence and development of glioma in Curcuma longa. Finally, we identified the active components 1-(1,5-Dimethyl-4-hexenyl)-4-methyl benzene and Zingiberene. At the same time, 190 target genes of Curcuma longa extracts on glioma were obtained using the Venn diagram. The results of GO analysis showed that the biological processes involved included a response to stimulation, metabolic process, inflammatory process, cell differentiation, and regulation of biological processes. KEGG analysis showed that the PI3K-Akt signaling pathway, MAPK signaling pathway, Th17 cell differentiation, and proteoglycan pathway might be involved in cancer. Further analyses showed that the IL-17 signaling pathway and Interleukin-4 and interleukin-13 signaling were involved in the inflammatory pathway. The analysis of key nodes showed that GSK3B, MAPK14, HSP90AA1, MAPK3 and MAPK8 were IL-17 signaling pathways, while HIF1A and JAK3 were Interleukin-4 and interleukin-13 signaling pathways. Conclusion: Curcuma longa extracts can regulate the occurrence and development of glioma by regulating the immune-inflammatory responses.

scholarly journals Arbuscular Mycorrhiza–Specific Signaling in Rice Transcends the Common Symbiosis Signaling Pathway

2008 ◽  
Vol 20 (11) ◽  
pp. 2989-3005 ◽  
Author(s):  
Caroline Gutjahr ◽  
Mari Banba ◽  
Vincent Croset ◽  
Kyungsook An ◽  
Akio Miyao ◽  
...  
Keyword(s):  
Arbuscular Mycorrhiza ◽  
Signaling Pathway ◽  
The Common

The common symbiotic signaling pathway

2019 ◽  
pp. 523-528
Author(s):  
Frédéric Debellé
Keyword(s):  
Signaling Pathway ◽  
The Common
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