Cellular receptor

Models also can assist in experimental design and the determination of the limits of experimental systems. For example, it is known that three proteins mediate the interaction of HIV with cells namely, the chemokine receptor CCR5, the cellular protein CD4, and the viral coat protein gpl20. An extremely useful experimental system to study this interaction is one in which radioactive CD4, prebound to soluble gpl20, is allowed to bind to cellular receptor CCR5. This system can be used to screen for... 

To obtain an increased intrinsic capacity to transgress biological membranes, a number of different modifications have been introduced to PNA. These modifications include conjugation of PNA to Hpophilic moieties [51, 97, 98], conjugation of PNA to certain so-caUed ceU-penetrating peptides [49, 55, 56, 66, 99-102] and conjugation to different moieties, which are supposed to be internahzed by specific cellular receptors [48, 103-105]. The work on cellular dehvery of PNA is, like the related work on ex vivo and in vivo effects of PNA, very difficult to summarize conclusively. First of all, the pronounced diversity of the reporter systems employed makes it impossible to directly compare the studies. Secondly, the widespread use of fluorescence studies in spite of the many inherent pitfalls of this technique makes it sometimes difficult to judge even qualitatively whether a presented result actually indicates cellular uptake. We have recently published a comprehensive review on cellular dehvery of PNA [82], with a more detailed assessment of the PNA dehvery hterature. 

Many environmental toxins interact with specific cellular receptors, including enzymes, ion channels and ion pumps, and thus provide natural tools for the study of cellular signalling pathways. Palytoxin, a compound isolated from the coelen-terate of genus Palythoa, is one such useful and intriguing compound. The structure of palytoxin was first determined in 1981 independently by Hirata (7) and Moore (2). As one of the most potent marine toxins known, palytoxin has been studied in a variety of systems ranging from erythrocytes to neurons. As a tumor promoter of the non 12-O-tetradecanoylphorbol-13-acetate (TPA) type, palytoxin can also be studied in the context of a growth control system. 

Stantchev TS, Broder CC. Human immunodeficiency virus type-1 and chemo-kines beyond competition for common cellular receptors. Cytokine Growth Factor Rev 2001 12(2-3) 219-243. 

Abraham G, Colonno RJ. Many rhinovirus serotypes share the same cellular receptor. J Virol 1984, 51 814-817. 

Phorbol esters are promoters that interact with cellular receptors and activate protein kinase C. Usually protein kinase C is activated by Ca++ and diacylglycerol, both of which result from the hydrolysis of phosphoinositides catalyzed by phospholipase C. Phospholipase C is normally activated by several different growth factors. Thus phorbol esters bypass a tightly regulated step in the control of cell growth. Since protein kinase C phosphorylates various proteins, it is not known how this activity participates in establishing a cancerous line of cells. 

Galardy, R.E. et al. (1978) Biologically active derivatives of angiotensin for labeling cellular receptors. J. Med. Chem. 21, 1279. 

Kull Jr., F.C., Jacobs, S., and Cuatrecasas, P. (1985) Cellular receptor for 1251-labeled tumor necrosis factor Specific binding, affinity labeling, and relationship to sensitivity. Proc. Natl. Acad. Sci. USA 82, 5756-5760. 

Epinephrine, a hormone made in the adrenal medulla and sympathetic nerve endings, calls for rapid mobilization of energy and glucose. Epinephrine, like glucagon, binds to specific cellular receptors and activates adenylate cyclase. For the most part, epinephrine can be considered... 

An, S., Dickens, M. A., Bleu, T., Hallmark, O. G. and Goetzl, E. J. Molecular cloning of the human EDG2 protein and its identification as a functional cellular receptor for lysophosphatidic acid. Biochem. Biophys. Res. Commun. 231 619-622, 1997. 

Before focusing our attention on PAF antagonists, it is important to consider the specific process with which they interfere the binding of PAF to its cellular receptors. 

The basis for this technique lies in the competition between the test antigen and a labelled antigen for the available binding sites on a fixed amount of antibody. While the binding sites are traditionally associated with an antibody, any source of specific reversible binding sites may be used to create an assay in this format. Examples of such are specific transport proteins such as thyroxine-binding globulin and certain cellular receptors such as opiate or benzodiazepine receptors. Under these circumstances the equilibrium mixture may be represented thus ... 

D10. Dumler, I. T., Petri, T., and Schleuning, W. D., Interaction of urokinase-type plasminogen activator (uPA) with its cellular receptor (uPAR) induces phosphorylation on tyrosine of a 38 kDa protein. FEBS Lett. 322, 37-40 (1993). 

The life cycle of HIV is typical of an enveloped retrovirus. As with other viruses, HIV requires a cellular receptor to infect a cell. The receptor for HIV is known as the CD4 antigen. The life cycle for HIV is outlined in Fig. 3. Virus replication is regulated by the products of six genes. 

Another potential class of antivirals is those that interfere with the ability of virus to enter cells. If the virus entry process is inhibited, then spread of infection within an individual might be inhibited. As discussed earlier, HIV virus particles initially attach to cells by way of the cellular receptor for CD4 protein, which is embedded in the surface of normal T lymphocytes and macrophages. Recently, recombinant DNA techniques have been used to make large amounts of a part of the pure CD4 protein. Test-tube experiments have shown that if this CD4 protein fragment is incubated with T lymphocytes or macrophages, it can saturate all the CD4 receptors and prevent subsequent infection with HIV. It is possible that this approach might be effective in people, as well. 

Analytical flow cytometry offers a rapid and facile means of monitoring cellular receptor content. For example, multiparameter flow cytometry techniques were used to monitor expression of GABAa receptor subunits during neurogenesis in embryonic rat brain (Marie et al., 2001). The content of the cell surface p75 neurotrophin receptor was measured in a heterogeneous population of mouse dorsal root sensory neurons, from which high and low p75 subsets were subsequently isolated by cell sorting (Barrett et al., 1998). 

Classical bacterial exotoxins, such as diphtheria toxin, cholera toxin, clostridial neurotoxins, and the anthrax toxins are enzymes that modify their substrates within the cytosol of mammalian cells. To reach the cytosol, these toxins must first bind to different cell-surface receptors and become subsequently internalized by the cells. To this end, many bacterial exotoxins contain two functionally different domains. The binding (B-) domain binds to a cellular receptor and mediates uptake of the enzymatically active (A-) domain into the cytosol, where the A-domain modifies its specific substrate (see Figure 1). Thus, three important properties characterize the mode of action for any AB-type toxin selectivity, specificity, and potency. Because of their selectivity toward certain cell types and their specificity for cellular substrate molecules, most of the individual exotoxins are associated with a distinct disease. Because of their enzymatic nature, placement of very few A-domain molecules in the cytosol will normally cause a cytopathic effect. Therefore, bacterial AB-type exotoxins which include the potent neurotoxins from Clostridium tetani and C. botulinum are the most toxic substances known today. However, the individual AB-type toxins can greatly vary in terms of subunit composition and enzyme activity (see Table 2). 

Keywords retroviruses, virus-cell interaction, cellular receptor, myo inositol transporter,... 

---