The N-Formylpeptide Chemotactic Receptor
Richard Horuk in Chemoattractant Ligands and Their Receptors, 2020
Phagocyte plasma membrane preparations exhibit GTP-sensitive fMLF binding, and fMLF-sensitive GTP hydrolysis and exchange, properties compatible with functional coupling of FPR to a heterotrimeric (αβγ) GTP binding regulatory protein or G protein.76,77 Upon binding ligand, FPR induces exchange of GDP for GTP by the G protein α subunit, resulting in dissociation of α from βγ subunits. A polyphos-phoinositide-specific phospholipase C (PLC) is then activated, probably by βγ sub-units, leading to the accumulation of inositol trisphosphate (IP3) and diacylglycerol in the cytoplasm. These products induce mobilization of calcium from intracellular stores and activation of protein kinase C, respectively.17 Since many distinct G protein subunits are known to exist, and the number of combinations that can at least theoretically combine to form the functional heterotrimer is very large, one important challenge is to determine which heterotrimers actually exist in phagocytes and are used by FPR. A more difficult issue is how receptor activation leads to G protein activation.
Pharmacological and Biochemical Changes in Airway Smooth Muscle in Relation to Bronchial Hyperresponsiveness
Devendra K. Agrawal, Robert G. Townley in Inflammatory Cells and Mediators in Bronchial Asthma, 2020
Airway smooth muscle contraction induced by neurotransmitters such as acetylcholine (ACh) or mediators such as histamine (HIS), prostaglandins, and leukotrienes (LTs) is initiated by the mobilization of calcium ions (Ca2+) into the cytoplasm of the cell, which may come from both extracellular and intracellular stores (Figures 1).33–38 It has recently been established that a receptor-induced metabolism of phosphoinositides in the plasma membrane may play a central role in these Ca2+ movements and the subsequent contraction of the muscle.39–46 The role of phosphoinositide metabolism as a transduction mechanism in cell signaling has recently been reviewed extensively.47 In short, receptor occupation by an agonist leads to activation of the enzyme phospholipase C (PLC) via a guanine nucleotide-dependent regulatory protein (Gp), causing enhanced hydrolysis of the membrane phospholipid phosphatidylinositol 4,5,-bisphosphate (PIP2) into two intracellular second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG), respectively (Figure 1).
Phosphatidylinositol and inositolphosphatide metabolism in hypertrophied rat heart
H. Saito, Y. Yamori, M. Minami, S.H. Parvez in New Advances in SHR Research –, 2020
Phospholipase C activity. The preliminary study determined that the optimal pH for phospholipase C (PI-PLC) was 7.0, and the substrate specificity of phospholipase C in hearts was previously determined (Kawaguchi and Yasuda, 1988a). Each subcellular fraction was incubated with [14C]arachidonic acid- labeled phospholipids (50,000 cpm/20 nmol) in 0.1 M Tris-HCl, pH 7.0, 5 mM CaCl2 for 2 min at 37°C. The released diacylglyceride (DAG) and free arachi-donic acid were extracted by the method of Folch et al. (1957). The chloroform phase was pooled and evaporated under vacuum. The residues were applied to thin-layer chromatography, which was developed in diethylether/acetic acid (96:4,vol/vol) and then again in a solvent system containing petroleum ether/ diethylether/acetic acid vol/vol/ vol) (Kawaguchi and Yasuda, 1986a). The respective spots of monoglyceride, diglyceride, triglyceride, and arachidonic acid were scraped, counted with a scintillation spectrometer, and analyzed according to previous studies (Kawaguchi and Yasuda, 1986b).
PLCG2 promotes hepatocyte proliferation in vitro via NF-κB and ERK pathway by targeting bcl2, myc and ccnd1
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Donghui Ma, Fang Lian, Xiaobai Wang
It is now well established that the metabolism of phospholipase plays an important role in a wide variety of cellular functions. The hydrolysis of phosphatidylinositol 4,5-bisphosphate by a specific phospholipase C (PLC) to two important second messengers, diacylglycerol and inositol 1,4,5-trisphosphate (Ins 1,4,5-P3), is one of the earliest key events triggered by a large number of extracellular signalling molecules. This effector role of PLC enzymes in signal transduction pathways has made them a subject of extensive research [1–4]. PI-PLC molecules have been found in a broad spectrum of organisms including bacteria, simple eukaryotes, plants and animals [5–9]. Studies of PI-PLC enzymes have included their catalytic properties, structure determination and, most extensively, their regulation through different signalling pathways [10] leading to different activities including proliferation, cell apoptosis, transformation, and tumor growth.
Role of the BMP6 protein in breast cancer and other types of cancer
Published in Growth Factors, 2021
Andrea Marlene García Muro, Azaria García Ruvalcaba, Lourdes del Carmen Rizo de la Torre, Josefina Yoaly Sánchez López
But, the role of BMP6 in cell lines proved to be interesting. Higher levels of BMP6 were found in the metastatic state and increased in cell migration (Joseph et al. 2012; Lu et al. 2017; Darby et al. 2008) and were associated with an EMT phenotype increment, bone metastases and faster progression also confirming the BMP6 participation in drug resistance when transcriptionally induced by phospholipase C (PLCɛ) (Yuan et al. 2019). The relationship of BMP6 with androgen receptor expression and cell proliferation (Yang et al. 2014) in the absence of androgens, WNT5A stimulated the expression of BMP6 and, successively, BMP6 increased cell proliferation, the authors confirmed the physical interaction of Smad 5 and β-catenin and their joint nuclear translocation in this pathway (Lee et al. 2014).
Characteristics and the role of purinergic receptors in pathophysiology with focus on immune response
Published in International Reviews of Immunology, 2020
Marharyta Zyma, Rafał Pawliczak
The subtypes of P2Y receptors consist of seven transmembrane domains with extracellular and intracellular loops [45].These receptors are split into two subclasses: those that couple to Gq and those that couple to Gi. The first subclass is P2Y1 subfamily that includes P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 receptors. Members of this subfamily are involved in regulation of phospholipase C. The second subclass is P2Y12 subfamily, which contains P2Y12, P2Y13, and P2Y14 receptors [24]. These receptors have a little sequence homology at the peptide level causing the differences in their functional and pharmacological characteristics. After activation of P2Y receptors come to activate phospholipase C leading to release of intracellular Ca2+ or activate the adenyl cyclase leading to changes in cAMP levels [2].
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