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CLOVES Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The PI3K heterodimer is activated by receptors with protein tyrosine kinase activity (RTK), and which then phosphorylates inositol ring 3′-OH group in inositol phospholipids, thus converting phosphatidylinositol-4,4-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3). This leads to the translocation and phosphorylation of protein serine/threonine kinase-3′-phosphoinositide-dependent kinase 1 (PDK1) to the cell membrane. PDK1 then phosphorylates Akt/PKB to initiate downstream processes involved in cell survival and cell cycle progression, including activation of mTOR, glycogen synthase kinase-3 (GSK3), p53, and IκB kinase (IKK), which is a positive regulator of survival factor NFκB, and inactivation of pro-apoptotic factors such as Bad and Procaspase-9 (Figure 88.1) [11,12].
Protein Function As Cell Surface And Nuclear Receptor In Human Diseases
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Urmila Jarouliya, Raj K. Keservani
Transforming growth factor-β (TGF-β) family, including TGF-β, activin, nodal, bone morphogenetic proteins (BMPs), and others, play vital roles in development, tissue homeostasis and some disease development [77]. This growth factor signal via protein (serine/threonine) kinase receptor, and Smad mediators to regulate a large number of biological processes, including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing or inflammation. TGF-β acts via specific receptors, activating multiple intracellular pathways resulting in phosphorylation of receptor-regulated Smad2/3 proteins that associate with the common mediator, Smad4. Such complex translocates to the nucleus, binds to DNA and regulates transcription of many genes. Furthermore, TGF-β-activated kinase-1 (TAK1) is a component of TGF-β signaling and activates mitogen-activated protein kinase (MAPK) cascades. Alterations of specific components of the TGF-β signaling pathway may contribute to a broad range of pathologies such as cancer, cardiovascular pathology, fibrosis, or congenital diseases. The knowledge about the mechanisms involved in TGF-β signal transduction has allowed a better understanding of the disease pathogenicity as well as the identification of several molecular targets with great potential in therapeutic interventions.
A serum miRNAs signature for early diagnosis of bladder cancer
Published in Annals of Medicine, 2023
Zuhu Yu, Chong Lu, Yongqing Lai
The function annotation of the target genes was analyzed with Enrichr database and illustrated in Figure 5. Go analysis revealed that these genes were mostly enriched in intracellular membrane-bounded organelle, nucleus, intracellular vesicle, cyclin/CDK positive transcription elongation factor complex, serine/threonine kinase complex. Molecular function of the target genes was enriched in regulation of transcription, cellular response to transforming growth factor beta stimulus. Biological process of the target genes involved was enriched in sequence-specific DNA binding, protein serine/threonine kinase activator activity, cyclin-dependent protein serine/threonine kinase activator activity, ubiquitin-like protein ligase binding. KEGG pathway analysis indicated the target genes enriched in FOXO signaling pathway, MAPK signaling pathway, Relaxin signaling pathway, Hepatocellular carcinoma, pathways in cancer. The functional annotation implied that target genes of the three miRNAs may be involved in proliferation and progression of bladder cancer.
Repair mechanism of Wuwei Fuzheng Yijing formula in di-2-ethylhexyl phthalate-induced sperm DNA fragmentation in mice
Published in Pharmaceutical Biology, 2022
Chenming Zhang, Shiqi Wang, Zulong Wang, Qi Zhang, Rubing Chen, Hao Zhang, Zhong Hua, Sicheng Ma
The 131 shared targets were run through the R language (R version 3.6.1) (R Foundation for Statistical Computing, Vienna, Austria), and then GO analysis was conducted to select the biological process (BP), cellular component (CC) and molecular function (MF) (Figure 4(A–C)). GO results showed that the shared gene sets were enriched in 2404 BP pathways, including response to oxidative stress (GO:0006979), peptidyl-serine modification (GO:0018209), gland development (GO:0048732), response to radiation (GO:0009314) and peptidyl-serine phosphorylation (GO:0018105). The shared gene sets were enriched in 84 CCs, including membrane raft (GO:0045121), membrane microdomain (GO:0098857), membrane region (GO:0098589), neuronal cell body (GO:0043025) and transcription factor complex (GO:0005667). The shared gene sets were enriched in 153 MFs, including protein serine/threonine kinase activity (GO:0004674), phosphatase binding (GO:0019902), protein tyrosine kinase activity (GO:0004713), ubiquitin-like protein ligase docking (GO:0044389) and endopeptidase activity (GO:0004175).
Differential expression of exosomal microRNAs in fresh and senescent apheresis platelet concentrates
Published in Platelets, 2022
Ziyue Mi, Li Gong, Yujie Kong, Peizhe Zhao, Yonghua Yin, Haixia Xu, Li Tian, Zhong Liu
Fifty-seven microRNAs were detected up-regulated. Figure 3A shows the GO analysis, the target genes are mostly enriched in transcription factor activity, RNA polymerase II core promoter sequence-specific DNA binding, DNA binding transcription factor activity, and protein serine/threonine kinase activity (molecular function); synapse, dendrite, and cell junction (cellular component); nervous system development, positive regulation of transcription from RNA polymerase II promoter, and positive regulation of cardiac muscle cell proliferation (biological process). And the KEGG analysis (Figure 3B) shows that the target genes are mainly involved in longevity regulating pathway, AMPK signaling pathway, relaxin signaling pathway, ErbB signaling pathway, and Ras signaling pathway, and taking part in axon guidance and parathyroid hormone synthesis, secretion, and activity, etc.