The diacylglycerol (DAG) mediated regulation of protein kinase C (PKC) family of serine/threonine

The lipids found in cell membranes belong to a class known as triglycerides, so called because they have one molecule of glycerol chemically linked to three molecules of fatty acids. The majority belong to one subgroup of triglycerides known as phospholipids. The cell membrane is made up of a phospholipid bilayer. The hydrophobic tails of the detergent molecules are taken up by this bilayer.

Introduction: The biological membranes are composed of phospholipid bilayers, each phospholipid with hydrophilic heads and hydrophobic tails, and proteins. This arrangement of the proteins and lipids produces a selectively permeable membrane. Many kinds of molecules surround or are contained within

The lipids found in the membrane are known as phospholipids. Phospholipids are fat derivatives in which one fatty acid has been replaced by a phosphate group and one of several nitrogen-containing molecules. The phospholipids’ structure is such that it appears to have a ‘head’ attached to a ‘tail’. The head section of the lipid is made of a glycerol group which is then attached to an ionised

Introduction: Cell membranes contain many different types of molecules which have different roles in the overall structure of the membrane. Phospholipids form a bilayer, which is the basic structure of the membrane. Their non-polar tails form a barrier to most water soluble substances. Membrane proteins serves as channels for transport of metabolites, some act as enzymes or carriers, while some are receptors. Lastly carbohydrate molecules of the membrane are relatively short-chain polysaccharides, which has multiple functions, for example, cell-cell recognition and acting as receptor sites for chemical signals.

Compound 3a was selected by the National Cancer Institute (NCI) USA for anticancer screening with the NCI code D-785902/1. Compound 3c was found in the already tested cancer candidates in the NCI data base under NCI code NSC: 650353[42]. Both candidates were screened on human tumour cell lines at 10-5 M at the 60-Cell-Line Screenings of the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI, Bethesda, Maryland, USA) under the drug discovery program of the NCI. The 60-cell-line-screening of the NCI includes 60 different tumour cell lines, the nine various organs and tumour types derived (leukaemia, non-small-cell lung cancer, colon cancer, CNS cancer, melanoma,

Several upstream kinases have been reported to activate AMPK, including liver kinase B 1 (LKB1) [12]. LKB1 is predominately localized in the nucleus under normal physiological condition, and is translocated to cytosol in response to stimulation, which leads to subsequent AMPK phosphorylation and activation [13]. When activated, AMPK decreases fatty acid levels by phosphorylating and thus inhibiting acetyl-CoA carboxylases (ACC), a critical enzyme for controling fatty acid biosynthesis and oxidation [14]. The activation of AMPK also decreases total cholesterol (TC) and triglyceride (TG) levels by inhibiting the activity of glycerol-3-phosphate acyltransferase (GPAT) and HMG-CoA reductase, respectively [15]. AMPK has therefore been proposed as a major therapeutic target for obesity and obesity-linked metabolic disorders such as hyperlipidemia and atherosclerosis [16]. 5-Aminoimidazole-4-carboxamide-1-b-D- ribofuranoside (AICAR) is one of the activators of AMPK

Regulation of DAG and phytoceramide by Ipc1. When Wild type and GAL7::IPC1 strains were exposed to galactose and glucose, DAG (activator of PKC1) levels in the GAL7::IPC1 strain increased when IPC1 was induced by galactose, and decreased when IPC1 was repressed by glucose. Furthermore, phytoceramide levels were increased when IPC1 was down regulated by glucose in the GAL7::IPC1 strain. In both wild type strains, no change was seen when IPC1 was up or down regulated, as expected (Fig. 2).

Sphingosine 1-phosphate, a product of sphingosine kinases (SphK), mediates various biological processes including cell proliferation, differentiation, motility, and apoptosis. Protein kinase C (PKC), is a family of protein kinase enzymes involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues.

I hypothesize that O-GlcNAcylation of specific sites on Sec24C/D regulate COPII vesicle trafficking and mediate protein-protein interactions. The experiments proposed below will test this hypothesis by completion of my three aims: 1) Determine how O-GlcNAcylation of Sec24C/D affects COPII vesicle secretion under normal and ER stress conditions, 2) Characterize Sec24C/D O-GlcNAc mediated protein-protein interactions and their role in vesicle trafficking and, 3) Examine the Interplay between O-GlcNAcylation and phosphorylation on Sec24C/D in cell cycle progression and vesicle trafficking.

Protein kinase C is a phospholipid-dependent kinase and the intracellular receptor for phorbol 12-myristate-13-acetate (PMA), a substance that activates both the respiratory burst and protein kinase C. PKC enzymes are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca2+) [1].

To fully understand the biological role of isoketals in oxidative injury and counter their detrimental effects, efforts to identify selective scavengers of isoketals were undertaken. A lead compound, pyridoxamine (PM) was first discovered as a carbonyl scavenger in 1996 by Billy G. Hudson and colleages (Booth, Khalifah et al. 1996), and identified through initial screens, where Amarnath and colleagues determined second-order reaction rates for a series of primary amines relative to N-α-acetyl-lysine (Amarnath, Amarnath et al. 2004). Pyridoxamine is a vitamer in the vitamin B6 family, and through our studies, PM was found to effectively intercept isoketals from adducting to cellular amines. Through the initial screen, pyridoxamine was found

both K-14585 and GB88 in that it requires minimal pre-incubation for antagonism of peptide/peptidomimetic activation of PAR2-dependent Ca2+ signaling and it acts as an antagonist for MAPK signaling pathways without any signs of activation up to the 100 M concentrations tested. C391 is the only published antagonist shown to be effective in blocking protease and peptidomimetic activation of PAR2 and we have further characterized this compound to demonstrate its effectiveness in blocking allergen protease-initiated signaling in human airway epithelial cells and in preliminary in vivo experiments (Approach Section). C391 will be the primary compound used in these studies. The development of receptor antagonists or agonists that differentially activate beneficial PAR2 signaling pathways and effectively bias against detrimental signaling events provides a novel route for asthma treatment.

The authors found that there was some variability in the expression and the splicing patterns of signaling molecules. From this variability, the authors focus on the Receptor tyrosine kinases (RTKs) because they are an important signaling molecules and is target for possible therapeutics. This variability could be a source for why some therapeutics that target RTKs are unsuccessful.

The substrates of glycerate kinase are ATP and D-glycerate and the products are ADP and 3-phospho-D-glycerate. This enzyme belongs to the family of transferases.1 Other common names include: glycerate kinase (phosphorylating), D-glycerate 3-kinase, D-glycerate kinase, glycerate-3-kinase, GK, D-glyceric acid kinase, and ATP: D-glycerate 2-phosphotransferase. 1 This enzyme participates in 3 metabolic pathways: serine/glycine/threonine metabolism, glycerolipid metabolism, and glyoxylate-dicarboxylate metabolism.1

The erythrocyte cell membrane comprises a typical lipid bilayer, similar to what can be found in virtually all human cells. Simply put, this lipid bilayer is composed of cholesterol andphospholipids in equal proportions by weight. The lipid composition is important as it defines many physical properties such as membrane permeability and fluidity. Additionally, the activity of many membrane proteins is regulated by interactions with lipids in the bilayer.