Phosphorylation cellular function

The first is cell injury (cytotoxicity), which can be severe enough to result in cell death. There are many mechanisms by which xenobiotics injure cells. The one considered here is covalent binding to cell macromol-ecules of reactive species of xenobiotics produced by metabolism. These macromolecular targets include DNA, RNA, and protein. If the macromolecule to which the reactive xenobiotic binds is essential for short-term cell survival, eg, a protein or enzyme involved in some critical cellular function such as oxidative phosphorylation or regulation of the permeability of the plasma membrane, then severe effects on cellular function could become evident quite rapidly. 

Post-translational modification of proteins plays a critical role in cellular function. For, example protein phosphorylation events control the majority of the signal transduction pathways in eukaryotic cells. Therefore, an important goal of proteomics is the identification of post-translational modifications. Proteins can undergo a wide range of post-translational modifications such as phosphorylation, glycosylation, sulphonation, palmitoylation and ADP-ribosylation. These modifications can play an essential role in the function of the protein and mass spectrometry has been used to characterize such modifications. 

Protein phosphorylation is one of the most important mechanisms in the regulation of cellular function. Proteins can be phosphorylated on serine, threonine or tyrosine residues. Most phosphorylation occurs on serine and threonine, with less than 1% on tyrosine (see Ch. 23). This perhaps accounts for the late discovery of tyrosine phosphorylation, which was found first on polyoma virus middle T antigen in 1979 by Hunter and colleagues [1,2]. 

C. The purpose of this question is to clarify the cellular mechanism of analgesia produced by morphine. First, morphine blocks the transmission of nociceptive impulses. In that case, the relevant question is how nociceptive impulses are transmitted via the release of pronociceptive neurotransmitters. The question then is to determine which intracellular process favors a block of release of neurotransmitters. The correct answer is C because calcium is required for neurotransmitter release. Blocking potassium efflux and increasing calcium channel phosphorylation produce functional depolarization and neurotransmitter release. Opioids are coupled to Gj (inhibitory proteins) that decrease cAMP. 

Diacylglycerol, on the other hand, is lipid soluble and remains in the lipid bilayer of the membrane. There it can activate protein kinase C (PKC), a very important and widely distributed enzyme which serves many systems through phosphorylation, including neurotransmitters (acetylcholine, a,- and P-adrenoceptors, serotonin), peptide hormones (insulin, epidermal growth hormone, somatomedin), and various cellular functions (glycogen metabolism, muscle activity, structural proteins, etc.), and also interacts with guanylate cyclase. In addition to diacylglycerol, another normal membrane lipid, phos-phatidylserine, is needed for activation of PKC. The DG-IP3 limbs of the pathway usually proceed simultaneously. 

The cellular functions of protein tyrosine phosphatases are closely associated with signal transduction via protein tyrosine kinases. The growth and differentiation promoting signals mediated by protein tyrosine kinases include autophosphorylations and phosphorylation of effector proteins (see 8.1.4). According to current ideas, the activity of protein tyrosine phosphatases may have a negative or positive influence on signal transduction via protein tyrosine kinases. On the one hand, protein tyrosine... 

Erythropoietin stimulates erythroid proliferation and differentiation by interacting with erythropoietin receptors on red cell progenitors. The erythropoietin receptor is a member of the JAK/STAT superfamily of cytokine receptors that use protein phosphorylation and transcription factor activation to regulate cellular function (see Chapter 2). Erythropoietin also induces release of reticulocytes from the bone marrow. Endogenous erythropoietin is primarily produced in the kidney. In response to tissue hypoxia, more erythropoietin is produced through an increased rate of transcription of the... 

Enzymes are sometimes inactive as simple polypeptides. Addition of another group forms the fully active enzyme. Phosphorylation or glycosylation of an OH or NH in an R-group is typical. Phosphorylations are especially common, and this process is itself mediated by another enzyme, called a kinase. Kinases are an important family of enzymes, and kinase inhibition can be a powerful means of impacting cellular function. 

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