Molecular characterization of protein kinase C delta (PKCδ)-Smac interactions

Holmgren, Christian; Cornmark, Louise; Lønne, Gry Kalstad; Masoumi, Katarzyna Chmielarska; Larsson, Christer

doi:10.1186/s12858-016-0065-x

Cited by 5 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased levels of calcium ions and PGE 2 may activate PKC-δ. Although the tyrosine phosphorylation of PKC-δ by thrombin is Ca 2+ -dependent [43], it is widely known that the activation of PKC-δ is Ca 2+ -independent, requiring only DAG [44][45][46]. In this study, NAD + may have activated PKC-δ through signals transferred from PGE 2 derived from DAG.…”

Section: Discussionmentioning

confidence: 72%

Exogenous NAD+ Stimulates MUC2 Expression in LS 174T Goblet Cells via the PLC-Delta/PTGES/PKC-Delta/ERK/CREB Signaling Pathway

Yeom

Lim

2020

Biomolecules

View full text Add to dashboard Cite

Background: MUC2, a major component of the mucus layer in the intestine, is associated with antimicrobial activity and gut immune system function. Currently, mucin is mainly known for its critical function in defense against toxic molecules and pathogens. In this study, we investigated the stimulatory effects of exogenous nicotinamide adenine dinucleotide (NAD + ) on the expression of MUC2 in LS 174T goblet cells. Methods: Genes related to MUC2 synthesis were measured by quantitative real-time PCR (qPCR). To analyze the gene expression profiles of NAD + -treated LS 174T goblet cells, RNA sequencing was performed. MUC2 expression in the cells and secreted MUC2 were measured by immunocytochemistry (ICC) and ELISA, respectively. Results: NAD + significantly stimulated MUC2 expression at mRNA and protein levels and increased the secretion of MUC2. Through RNA sequencing, we found that the expression of genes involved in arachidonic acid metabolism increased in NAD + -treated cells compared with the negative control cells. NAD + treatment increased phospholipase C (PLC)-δ and prostaglandin E synthase (PTGES) expression, which was inhibited by the appropriate inhibitors. Among the protein kinase C (PKC) isozymes, PKC-δ was involved in the increase in MUC2 expression. In addition, extracellular signal-regulated kinase (ERK)1/2 and cyclic AMP (cAMP) response element-binding protein (CREB) transcript levels were higher in NAD + -treated cells than in the negative control cells, and the enhanced levels of phosphorylated CREB augmented MUC2 expression. Conclusions: Exogenous NAD + increases MUC2 expression by stimulating the PLC-δ/PTGES/PKC-δ/ERK/CREB signaling pathway.Biomolecules 2020, 10, 580 2 of 18 contribute to chronic inflammation in the intestine [3]. Therefore, conservation of an intact mucus layer that properly regulates immune responses is a main factor that is necessary for the maintenance of intestinal homeostasis and the prevention of intestinal inflammatory diseases.MUC2 gene expression is regulated by cyclic AMP (cAMP) response element-binding protein (CREB) in retinoic acid-treated normal human tracheobronchial epithelial (NHTBE) cells [4]. CREB is a transcription factor regulating the expression of genes involved in a variety of cellular processes, such as cell growth and survival, differentiation, and mucin production [5]. Upon cAMP-induced phosphorylation through intracellular signaling cascades, CREB is activated and stimulates gene transcription by binding to the promoters of target genes. CREB phosphorylation through the mitogen-activated protein kinase (MAPK) signaling pathway is associated with various human diseases [5]. For example, angiotensin II induces cardiac fibrosis by enhancing periostin expression via the p38 MAPK-CREB pathway [6]. The protein kinase C (PKC)/p38 MAPK/CREB pathway is involved in membrane wound repair [7]. An E3 ubiquitin ligase (CUL4A) promotes the proliferation of cancer cells through the phosphorylation-mediated activation of ERK1/2 followed by CREB [8]. Paeoniflorin, der...

show abstract

Section: Discussionmentioning

confidence: 72%

Exogenous NAD+ Stimulates MUC2 Expression in LS 174T Goblet Cells via the PLC-Delta/PTGES/PKC-Delta/ERK/CREB Signaling Pathway

Yeom

Lim

2020

Biomolecules

View full text Add to dashboard Cite

show abstract

“…PRKCD is known to be an important regulator of apoptosis 27 . ATM was related to DNA damage response, and utilization of ATM inhibitors may provide a novel anti-cancer treatment strategy.…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Biomarkers and Immunotherapeutic Targets with CXC Chemokines in Glioblastoma Multiforme Using Integrated Bioinformatic Analysis

Liu¹,

Zhu²,

Wang³

2020

Preprint

View full text Add to dashboard Cite

Background Glioblastoma multiforme (GBM) is the most malignant central nervous system tumour bearing a dismal prognosis. The study aimed to explore the potential biomarkers and therapeutic targets with CXC chemokines in GBM by integrated bioinformatics analysis.Methods Differentially expressed CXC Chemokines were identified in GBM using GEPIA and UALCAN databases,and Kaplan–Meier analyses were performed by GEPIA subsequently. Protein -protein interaction (PPI) network was established in STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to analyze differentially expressed CXC Chemokines and their similar genes gained from GEPIA. Then, we conducted transcription factors, kinase targets, and immune cells infiltration using TRRUST, LinkedOmics, and TIMER, respectively.Results The mRNA expression levels of CXCL3/5/6/9/10/11/12/13/16 in GMB were significantly elevated compared to normal tissues. GBM patients with higher transcriptional levels of CXCL5/6 were significantly associated with worse disease-free survival, while higher transcriptional levels of CXCL3/5/8 were significantly related to worse overall survival. The functions of CXC chemokines were enriched in Chemokine signaling pathway, Cytokine-cytokine receptor interaction, IL-17 signaling pathway, et.al. RELA and NFKB1were key transcription factors of CXC chemokines. The kinase targets of CXC chemokine contained CDK1, CDK2, PRKCD, MAPK14, ATM, LCK, MTOR, and GRK3, which are involved in oncogenesis, migration, and survival. Moreover, we revealed significant correlations between the expression of CXC chemokines and the infiltration immune cells, especially for dendritic cells.Conclusion The significant CXC chemokines and related pathways may provide a novel possibility for prognostic biomarkers and immunotherapeutic treatment in GMB.Short title: CXC Chemokines with prognosis in GBM

show abstract

“…Other prosurvival mechanisms include sequestration of Smac, an antagonist of inhibitor-of-apoptosis proteins ( Fig. 4 A ) ( 234 , 235 ), and regulation of the phosphorylation and inactivation of the proapoptotic protein Bim (BCL-2-like protein 11) ( 236 , 237 ) ( 186 , 198 , 237 ).…”

Section: Cell Survival and Cell Deathmentioning

confidence: 99%