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Klebsiella: Caenorhabditis elegans as a Laboratory Model for Klebsiella pneumoniae Infection
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Arumugam Kamaladevi, Krishnaswamy Balamurugan
The p38 MAPK is a multistep mechanism that includes immune regulators like NSY-1/SEK-1/PMK-1 MAP kinase pathway, which was identified through forward genetics using mutants that had enhanced susceptibility to infection with Gram-negative bacteria P. aeruginosa [58]. This pathway is orthologous to the ASK1 (MAP kinase kinase kinase)/MKK3/6 (MAP kinase kinase)/p38 (MAP kinase) pathway in mammals, and its identification in C. elegans provided a deeper knowledge on host perspective. The p38 MAP kinase pathway acts cell-autonomously in the intestinal epithelium [59] to coordinate immune defense against a wide variety of ingested pathogens. C. elegans having a loss-of-function mutations in pmk-1 are hypersusceptible to infection by Gram-negative pathogens such as P. aeruginosa [58,60], S. entrica [61], Y. pestis [62], and S. marcescens [63]; Gram-positive pathogens E. faecalis [63] and Staphylococcus aureus [33]; and the fungus C. albicans [64,65]. Nematodes’ global transcriptional profiling analyses revealed that PMK-1 regulates the expression putative antimicrobial effectors, including C-type lectins, Shk toxins, and CUB-like domain [58], in the absence of microbial challenge, and this is termed as “basal regulation.”
Tumor Suppressor Genes and Oncogenes
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
Many cell surface receptors for growth factors contain a tyrosine kinase domain as part of the protein, which is similar to the src family of oncogene tyrosine kinase (including Src, Yes, Fgr, Lck, Lyn, Hck, and Blk) and contain SH2 domains facing the internal portion of the cell. Other growth factor receptors are closely associated with separate tyrosine kinase proteins that are not an intrinsic part of the receptor protein itself. Most of the transforming growth factor receptors [EGFr, insulin-like growth factor I receptor (IGF-Ir), nerve growth factor receptor (NGFr), platelet-derived growth factor receptor (PDGFr), fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor receptor (VEGFr)] contain an intrinsic tyrosine kinase domain, with an exception for transforming growth factor-β (TGF-β), which contains a serine/threonine kinase. When activated by ligand binding, tyrosine kinase receptors autophosphorylate at several phosphorylation sites and can then act as docking sites for a small set of intracellular proteins that recognize tyrosine-associated phosphate sites via their SH2 domains (such as SOS and GrB2). Activation of the EGFr produces dimerization of the receptor, autophosphorylation of tyrosine residues, and phosphorylation of target proteins. EGFr activation is linked to the ras signal transduction pathway via two proteins (Sos and Grb2), which, when EGFr is activated, link via Raf (MAP kinase kinase kinase) to the downstream signals of the ras pathway such as MAP kinase.
REGULATORY MECHANISMS
Published in David M. Gibson, Robert A. Harris, Metabolic Regulation in Mammals, 2001
David M. Gibson, Robert A. Harris
The active form of Ras binds to the first of a series of linked protein kinases that phos-phorylatc (activate) and are themselves phosphorylatcd (activated) on specilic serine, tyrosine or threonine residues. The sequence, as indicated in Figure 3.8, shows Raf-I, Mck and MAPK(FRK) which are activated in response to insulin (thus I RK for "endocrine receptor kinase"). They are representatives of three large families of kinases found in the various differentiated cells of the organism: MKKK (mitogen activating protein kinase kinase kinase), MKK (mitogen activating protein kinase kinase) and МАРК (mitogen activating protein kinase), respectively. The three interlocked kinases are ordinarily found grouped together by scalTolding proteins, constituting a Raf-MAPK pathway module. All of these kinase activities are opposed by protein phosphatases.
Transforming growth factor-β signalling pathway in tendon healing
Published in Growth Factors, 2022
Yujie Li, Xinyue Liu, Xueli Liu, Yuanqiu Peng, Bin Zhu, Sheng Guo, Chenglong Wang, Dingxuan Wang, Sen Li
Apart from the activation of Smad-dependent cascades, TGF-β can signal in a noncanonical fashion as well. TGF-β can activate all three known MAPK pathways: extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and c-Jun-N-terminal kinase (JNK).The MAPK pathway contains a three-stage kinase cascade, including MAP kinase (MAPKKK, MAP3K, MEKK or MKKK), MAP kinase (MAPKK, MAP2K, MEK or MKK), and MAPK (Qi and Elion 2005). As well as TGF-β can activate TAK1 in the MAPK signalling pathway, and TAK1 can phosphorylate and activate IkB kinase, thereby stimulating NF-κB signalling, so TGF-β signaling may induce NF-κB signalling(Derynck and Zhang 2003)(Figure 2).
β-arrestin 2 quenches TLR signaling to facilitate the immune evasion of EPEC
Published in Gut Microbes, 2020
Zijuan Chen, Ruixue Zhou, Yihua Zhang, Doudou Hao, Yu Wang, Shichao Huang, Ningning Liu, Chunmei Xia, Nissan Yissachar, Feng Huang, Yiwei Chu, Dapeng Yan
K63-linked ubiquitination of TAK1 leads to the formation of the TRAF6–TAK1–MAP kinase kinase kinase 3 (MEKK3) complex, which contributes to sustained activation of NF-κB.28,29 Using lysates of HEK293 T cells expressing TAK1, TAB1, and a plasmid-expressing ubiquitin, K63-linked ubiquitin, or K48-linked ubiquitin, we found that SHP-1 inhibited total or K63-linked ubiquitination, but had no effect on K48-linked ubiquitination of TAK1 (Figure 5(f,g), Figure S7 C). Using the dual-luciferase reporter assay system, we found that SHP-1 inhibits the activation of NF-κB and MAPK signaling pathways triggered by TAK1/TAB1 (Figure 5(h,i)).
BRAF inhibitors and their immunological effects in malignant melanoma
Published in Expert Review of Clinical Immunology, 2022
Rebecca Adams, Jack E M Coumbe, Ben G T Coumbe, Jennifer Thomas, Zena Willsmore, Marija Dimitrievska, Monica Yasuzawa-Parker, Maximilian Hoyle, Suhaylah Ingar, Jenny L C Geh, Alastair D MacKenzie Ross, Ciaran Healy, Sophie Papa, Katie E Lacy, Sophia N Karagiannis
The pathway is arranged in three tiers containing sequentially acting serine threonine kinases: MAP kinase kinase kinase (MAPKKK), MAP kinase kinase (MAPKK), and a downstream effector MAP kinase (MAPK) [20]. Sequential phosphorylation of these kinases (outlined in Figure 1) leads to the phosphorylation of downstream targets in the cytosol and nucleus, which mediate biological responses [18]. To prevent persistent activation of MAPK, upstream negative feedback occurs. In the absence of RTK-ligand engagement, members of the MAPK pathway remain in their non-phosphorylated, inactive states, preventing downstream signaling.