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Articular Cartilage Development
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
Generally, the MAPK pathways are composed of three sequential signaling molecules/kinases, the MAPK, the MAPK kinase (MAPKK), and the MAPK kinase kinase (MAPKKK or MAP3K). These commonly tie G protein-coupled receptors (GPCRs) into the pathway. The MAPKs respond to stress cytokines, either pro-inflammatory or mitogenic, to activate through a cascade of phosphorylation events and eventual transcriptional activity (Pouyssegur et al. 2002; Chong et al. 2003; Chadee and Kyriakis 2004). Specifically, the generic pathway consists of a stimulus activating a MAP3K, which activates a MAPKK, which activates a MAPK, which induces a response, commonly modulation of gene expression. However, MAPK phosphorylates multiple substrates other than transcription factors, including cytoskeletal proteins and phospholipases. Each of these steps results in an amplification of the signal induced by the initial stimuli. These kinase pathways function through phosphorylation events of individual signaling members. Significant crosstalk between the pathways has been observed, with some MAPKKs being activated by multiple MAP3Ks (Junttila et al. 2008). The exact role some member proteins play in activation of specific pathways remains unclear, although scaffolding proteins have been identified that modulate the specificity of pathway activation (Kolch 2005; Sacks 2006).
Reduction and Fixation of Sacroiliac joint Dislocation by the Combined Use of S1 Pedicle Screws and an Iliac Rod
Published in Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White, Advances in Spinal Fusion, 2003
Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White
The ERK cascade is activated when cells encounter signals to proliferate. Recent investigations have demonstrated TGF-β1 activation of the MAPK signaling cascade [26,27]. This cascade begins with the activation of MAPK-kinase-kinase (MAPKKK), or RAF, through a poorly defined mechanism that usually involves the membrane-bound, small G-protein, RAS [25,28]. Activated RAF then phosphorylates and thus activates MAPK-kinase (MAPKK), or MEK, that has the unique ability to phosphorylate ERK on a specific threonine-glutamic acid-tyrosine activation motif [25,29]. ERK phosphorylation/activation allows for translocation to the nucleus, where it can interact with its nuclear targets, namely transcription factors and the basal transcription complex [30,31].
Molecular Approaches for Enhancing Abiotic Stress Tolerance in Plants
Published in Hasanuzzaman Mirza, Nahar Kamrun, Fujita Masayuki, Oku Hirosuke, Tofazzal M. Islam, Approaches for Enhancing Abiotic Stress Tolerance in Plants, 2019
Sushma Mishra, Dipinte Gupta, Rajiv Ranjan
In addition to the aforementioned responses, mitogen-activated protein kinase (MAPK) cascade gets activated in response to ROS generation following abiotic stresses. It consists of a series of phosphorylation-activation relay system, mediated by three protein kinases: MAPKKK–MAPKK–MAPK; i.e., a stimulus is perceived by a MAP kinase kinase kinase (MAPKKK), which activates a MAP kinase kinase (MAPKK), and finally the signal is transmitted to their downstream target via a MAP kinase (MAPK) (Mittler, 2002). Generally, the downstream target is a TF whose activity, localization or stability would be affected by the phosphorylation (Sinha et al., 2011; Jaspers and Kangasjärvi, 2010). Overexpression of Nicotiana protein kinase 1 (NPK1), a MAPKKK, in several crop species resulted in increased tolerance to freezing, heat, salt and drought stress (Banno et al., 1993; Kovtun et al., 2000). Transgenic maize over-expressing NPK1 under the control of a constitutive promoter activated an oxidative stress signaling pathway (involving glutathione-S-transferases (GSTs), HSPs, peroxidases and catalases), which led to enhanced tolerance to drought stress, by protecting the photosynthetic machinery of plants from damage. The transgenics also showed increased kernel weight, comparable to that of well-watered plants (Shou et al., 2004). Two Arabidopsis MAPKs, ATMPK4 and ATMPK6, are also activated by environmental stresses such as low temperature, low humidity, hyper-osmolarity, touch and wounding (Ichimura et al., 2000). Similar reports involving the role of the MAPK pathway in abiotic stresses have been documented in other species as well (Taj et al., 2010; Zhang et al., 2016).
Targeting gap junctional intercellular communication by hepatocarcinogenic compounds
Published in Journal of Toxicology and Environmental Health, Part B, 2020
Kaat Leroy, Alanah Pieters, Andrés Tabernilla, Axelle Cooreman, Raf Van Campenhout, Bruno Cogliati, Mathieu Vinken
Polycyclic aromatic hydrocarbons (PAHs) are toxic environmental pollutants that act through the aryl hydrocarbon receptor (AhR) (Kabatkova et al. 2015), a receptor controlling migration, proliferation, cell adhesion and cell-cell communication (Andrysik et al. 2013). PAHs with lower molecular weight, consisting of maximum 4 benzene rings, are less genotoxic compared to PAHs that consist of at least 5 benzene rings. The former, however, inhibit GJIC and disrupt contact inhibition, and are therefore involved in tumor promotion (Kabatkova et al. 2015). In rat epithelial cells, PAHs reduce Cx43 levels and gap junction plaques, possibly through upregulated proteasomal degradation (Andrysik et al. 2013). GJIC is inhibited through phosphatidylcholine-specific phospholipase C (PC-PLC) and MAPK/extracellular signal-regulated kinase (ERK) pathways, but not through mitogen-activated protein kinase kinase (MEK) mechanisms (Sovadinova et al. 2015; Upham et al. 2008).
Core genes in lung adenocarcinoma identified by integrated bioinformatic analysis
Published in International Journal of Environmental Health Research, 2023
Liu Yang, Qi Yu, Yonghang Zhu, Manthar Ali Mallah, Wei Wang, Feifei Feng, Qiao Zhang
The PI3K-AKT pathway is one of the key signaling pathways involved in proliferation, migration and invasion of lung cancer cells (Jiang et al. 2020). It has been noted that aberrant activation of PI3K-AKT pathway is related to cancer tumorigenesis and progression (Mayer and Arteaga 2016). We found that six genes (ANGPT1, TEK, COL1A1, SPP1, THBS2 and VWF) involved in PI3K-AKT pathway (Figure 8). COL1A1, SPP1, THBS2 and VWF in extracellular matrix (ECM) activate focal adhesion kinase (FAK) by binding to integrin (ITGA and ITGB), which activates the PI3K/AKT signaling in turn. As a growth factor, ANGPT1 activates the PI3K/AKT and MEK/ERK signaling pathways by combining with TEK receptor tyrosine kinase. Club cell secretory protein (CC16) is encoded by the SCGB1A1 gene (Almuntashiri et al. 2020). Studies have showed that SPARCL1 (Ma et al. 2018) and CC16 (Zhou et al. 2019) can inhibit the transduction of mitogen‑activated protein kinase kinase (MEK)/extracellular signal‑related kinase (ERK) signaling. Previous studies demonstrated that hepatic stellate cells (HSCs)-derived cartilage oligomeric matrix protein (COMP) collaborated with CD36 and subsequently activate MEK/ERK and PI3K/AKT signaling pathways (Li et al. 2018). Stromal cell-derived factor 1 (SDF-1) could induce PECAM-1 through Src family tyrosine kinases to enhance the chemotactic signaling pathway involving PI3K/AKT/mTORC1 (Umezawa et al. 2017). Core genes could affect cell survival, migration, proliferation and metabolism by activating or inhibiting the PI3K-AKT signaling pathway. Taken together, we speculated that core genes may modulate LUAD through PI3K-AKT pathway.
Epigenetic modifications associated with pathophysiological effects of lead exposure
Published in Journal of Environmental Science and Health, Part C, 2019
Madiha Khalid, Mohammad Abdollahi
A study with rat neonates displayed a period of transient expression of APP mRNA upon 200 ppm Pb exposure followed by the period of their overexpression along with increased Sp1 activity, long after 20 months when Pb exposure was ceased. All this evidence suggests that Pb is capable of affecting APP expression and regulation later in life, potentially resulting in amyloidogenesis.153 The mitogen-activated protein kinase (MAPK) signaling pathway is vital for axon, and synapse function, neural development, and regeneration.77,251,252 The binding of Sp1 to its specific DNA sequence is regulated by protein kinase C (PKC). Such signal transduction pathways are sensitive to exposure of Pb and similar heavy metals,253,254 suggesting other mechanisms of Pb-induced tauopathies. Developmental Pb exposure in mice with 0.1 or 2 mM Pb levels caused an increased neurofilament phosphorylation, glial fibrillary acidic protein, myelin basic protein and neuronal structural protein, resulting in impaired axonal transport and function.77 In another study, microarray analysis revealed upregulated miRNAs in rats with all, i.e., 100, 200, and 300 ppm Pb exposure levels. However, significantly decreased expression in miR-494 (P < 0.05) was observed, with significantly increased expression of miR-211, -449a, -34c/b, and -204 at the 300 ppm Pb exposure level. Furthermore, all Pb exposure levels showed a declined expression of Bcl-2, inositol 1,4,5-triphosphate receptor type 1 (Itpr1), mitogen-activated protein kinase kinase 1 (Map2k)1 mRNAs and their corresponding proteins. Such declines were observed to be significant at 300 ppm Pb, along with repressed Bcl-2/Bax ratio (P < 0.01). According to the bioinformatics analysis, the changed miRNAs expression was mostly related to neural development, regeneration, neural injury, axon, and synapse function. All these evidence showed that Pb altered the expression of various miRNAs, suggesting downstream effects on their targets, related genes and associated pathways (Figure 4).255