Cell-signaling

Linder JU, Schultz JOB (2003) The Class III adenylyl cyclases multi-purpose signalling modules. Cell Signal 15 1081-1089... 

Masri B, Knibiehler B, Audigier Y (2005) Apelin signalling a promising pathway from cloning to pharmacology. Cell Signal 17 415-426... 

Phosphatidylinositol (abbreviated Ptdlns, or PI) is a minor class of phospholipids composed of glycerol, fatty acids and inositol. Pis are found in the cytosolic side of eukaryotic cell membranes. They are substrates fora large number of enzymes which are involved in cell signalling. 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

Since the SUMO pathway affects multiple pathways ranging from transcription, DNA repair, and intracellular trafficking over cell signaling and cell cycle control to basic metabolism, it is not suiprising that links to diseases and viral assaults are emerging. However, the field is not yet at a stage sufficiently developed for pharmacological intervention. Below we will describe selected examples for links of the SUMO pathway to diseases and viral functions. 

The infectious cycle of a (+)-strand RNA virus such as the hepatitis C virus differs by the fate of the viral RNA genome in the infected cell. Upon entry into the cell, the HCV genome is used as a messenger RNA to drive the synthesis of a large polyprotein precursor of about 3,000 residues [2]. The structural proteins are excised from the precursor by host cell signal peptidase. 

Genes implicated in cell signaling and cell cycle regulation (for examples see text)... 

Azzi A, Gysin R, Kempna P et al (2004) Vitamin E mediates cell signaling and regulation of gene expression. Ann N YAcad Sci 1031 86-95... 

TBT and TFT are membrane-active molecules, and their mechanism of action appears to be strongly dependent on organotin(IV) lipophilicity. They function as ionophores and produce hemolysis, release Ca(II) from sarcoplasmic reticulum, alter phosphatodylseiine-induced histamine release, alter mitochondrial membrane permeability and perturb membrane enzymes. Organotin(IV) compounds have been shown to affect cell signaling they activate protein kinase and increase free arachidonic acid through the activation of phospholipase... 

Newgard CB, McGarry JD Metabolic coupling factors in pancreatic beta-cell signal transduction. Annu Rev Biochem 1995 64 689. 

Merrill AH, Sweeley CC Sphingolipids metabolism and cell signaling. In Biochemistry of Lipids, Lipoproteins and Membranes. Vance DE, Vance JE (editors). Elsevier, 1996. 

A one-stop overview for the specialist or nonspecialist of what is happening in cell signaling.)... 

Fruifs and vegetables also contain ofher bioactive substances such as polyphenols (including well-known pigments anthocyanins, flavonols) and non-provitamin A carotenoids (mainly lycopene, lutein, and zeaxanthin) that may have protective effects on chronic diseases. Polyphenols and carotenoids are known to display antioxidant activities, counteracting oxidative alterations in cells. Besides these antioxidant properties, these colored bioactive substances may exert other actions on cell signaling and gene expression. 

In addition, it is becoming increasingly apparent that low-level fluxes of ROM may have cell-signalling roles. The action of NO has been described above, whilst the ROM-mediated control of the transcription nuclear factor (NF-xB) is detailed below. 

The effect of prolonged antioxidant therapy in relation to normal physiological processes (for example, redox cycling, cell-cell signalling, transcription factor activation) must be assessed. It is conceivable that the overload of one antioxidant by dietary supplementation (for example, a-tocopherol) may shift the levels of other antioxidants (for example, by decreasing ascorbate and /3-carotene concentrations), with unknown consequences. To assess the potential for lipid-soluble antioxidant treatment in inflammatory diseases such as RA, further investigations into these questions will be needed. 

Protein kinase C theta plays a critical role in T cell signaling and thus the inhibition of this enzyme has the potential to be useful for treating inflammatory diseases. Cywin et al. [55] describe the parallel optimization of potency against the enzyme,... 

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