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Dermal filler complications and management
Published in Michael Parker, Charlie James, Fundamentals for Cosmetic Practice, 2022
Degranulation is, in essence, the release of said granular contents from within a cell to its surrounding environment. Regarding anaphylaxis, the mechanism of release is through a tyrosine-kinase phosphorylation cascade after a pro-inflammatory cell (such as a mast cell) has been activated by an IgE-antigen complex. The relevance of a phosphorylation cascade is that through enzymatic phosphorylation a small signal can be rapidly and significantly amplified via a short series of chemical reactions. This phosphorylation cascade results in an influx in intracellular calcium, which in itself is the trigger for degranulation to occur. When mast cells degranulate, they release pro-inflammatory mediators such as histamine, prostaglandin and cytokines such as TNF-α. See Figure 13.5.
Biochemical Adaptations to Early Extrauterine Life
Published in Emilio Herrera, Robert H. Knopp, Perinatal Biochemistry, 2020
José M. Medina, Carlos Vicario, María C. Juanes, Emilio Fernández
Immediately after delivery, the fall in the insulin/glucagon ratio triggers liver glycogenolysis in order to supply neonatal tissues with glucose for both general and specific purposes (see Section II). Activation of glycogenolysis is achieved by phosphorylation of glycogen phosphorylase through the phosphorylation cascade that is switched on by the increase in cAMP levels (Figure 3). It is very intriguing, however, that the synthesis of glucose 6-phosphatase, a compulsory enzyme for the output of glucose from liver glycogen, is delayed in the rat, being fully active at the middle of the suckling period.12 Since glycogenolysis is very active 2 h after delivery (Figure 4) other enzymes would be responsible for early postnatal glycogenolysis. This may be the case of lysosomal α-glycosidase which has been claimed to be involved in neonatal glycogenolysis.6
p21ras and Receptor Signaling
Published in Juan Carlos Lacal, Frank McCormick, The ras Superfamily of GTPases, 2017
Boudewijn M. Th. Burgering, Johannes L. Bos
A link between the phosphorylation cascade and insulin-induced changes in lipid metabolism may be provided by the observation that insulin directly tyrosine phosphorylates and activates PI-3 kinase.93,94 This kinase phosphorylates (poly)phosphatidylinositols on the 3-position of the inositol ring. The biological function of this molecule is unclear, however.
A pinitol-rich Glycyrrhiza glabra L. leaf extract as functional supplement with potential in the prevention of endothelial dysfunction through improving insulin signalling
Published in Archives of Physiology and Biochemistry, 2022
Laura Siracusa, Cristina Occhiuto, Maria Sofia Molonia, Francesco Cimino, Marco Palumbo, Antonella Saija, Antonio Speciale, Concetta Rocco, Giuseppe Ruberto, Mariateresa Cristani
IRS-1 protein phosphorylation is a determining factor for the insulin signal transduction. In physiological conditions, the binding of insulin to its membrane receptor (IR) triggers the autophosphorylation of tyrosine residues and leads to a series of phosphorylation cascade involving the activation of the IRS/PI3K/Akt/eNOS pathway. One of the most evident effects of insulin resistance is the impairment of the activation of this signalling pathway. This impairment leads to a decreased NO production and increased endothelin 1 (ET-1) secretion. High levels of circulating cytokines or FFAs cause drastic changes in insulin pathway and in particular induce IRS-1 phosphorylation at the serine site and inhibit IRS-1 tyrosine phosphorylation, thus blocking the PI3K/Akt/eNOS pathway with subsequent insulin resistance (Gual et al. 2005). In the current study, we investigated the effects of PA-induced insulin resistance by focussing on Tyr895 phosphorylation of IRS-1 protein as a key regulator step in insulin signal transduction. Figure 4 shows that insulin-induced phosphorylation at Tyr895 site of IRS-1 was negatively affected by the exposure of endothelial cells to PA. Both GGLME (in a dose-dependent way) and d-pinitol pre-treatments were associated to an increased Tyr895 phosphorylation of IRS-1. Finally, the treatment of GGLME or d-pinitol alone was associated to an increase of IRS-1 Tyr895 phosphorylation with respect to controls.
Overcoming challenges in developing small molecule inhibitors for GPVI and CLEC-2
Published in Platelets, 2021
Foteini-Nafsika Damaskinaki, Luis A. Moran, Angel Garcia, Barrie Kellam, Steve P. Watson
The clustering of GPVI and CLEC-2 drives intracellular signaling cascades that lead to activation of platelets. GPVI is a single transmembrane protein belonging to the immunoglobulin family of receptors that is expressed in the membrane with the dimeric Fc receptor (FcR) γ-chain, with each chain having an immunoreceptor tyrosine-based activation motif (ITAM), characterized by two conserved YxxL sequences [29]. In contrast, the single transmembrane, lectin-like receptor, CLEC-2, has one YxxL sequence in its cytosolic tail, named a hemITAM (or hemi-ITAM) [30]. Clustering of GPVI or CLEC-2 leads to phosphorylation of the conserved tyrosines in the hemITAM or ITAM sequence by Src and Syk tyrosine kinases, leading to binding of the tandem SH2 domains in Syk and initiation of a downstream signaling cascade orchestrated through the protein adapter LAT. This acts as a binding template for other proteins facilitating a phosphorylation cascade, including various adapter and effector proteins, leading to activation of PI 3-kinase and PLCγ2 (Figure 1). PI 3-kinase generates the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) which binds to pleckstrin homology and SH2 domains. PLCγ2 generates the second messenger inositol 1,4, 5-trisphosphate (IP3) and 1,2-diacylglycerol, which release Ca2+ and activate protein kinase C, respectively.
Advances, challenges and tools in characterizing bacterial serine, threonine and tyrosine kinases and phosphorylation target sites.
Published in Expert Review of Proteomics, 2019
Giovanni J. Pagano, Ryan J. Arsenault
Much like the two-component system, the phosphotransferase system (PTS) involves a series of phosphate transfers between enzymes, allowing for the transport of sugars across the cell membrane. Phosphoenolpyruvate (PEP) first provides a phosphate group to a histidine on the cytosolic protein Enzyme I (EI), which then transfers the phosphate to a histidine on cytosolic HPr. This is followed by the phosphorylation cascade of proteins in the Enzyme II (EII) system, generally EIIA, EIIB and membrane-bound EIIC. The terminal step transfers the phosphate to a sugar for transport into the cell, where it can be metabolized. EI and HPr are general components utilized for all transfers, while the Enzyme II system components are specific for single sugars or small families of carbohydrates [8].