Other Receptor Classes

The cell has other transmembrane receptors and signaling pathways that do not fit into the. .classical receptor types and signal mechanisms described in Chapters 5-11. The following signaling pathways certainly do not complete the list of intercellular and intracellular commimication mechanisms in mammals, and it is to be expected that other classes of signaling pathways will be described in the future. 

1 Receptors with Intrinsic Ser/Thr Kinase Activity the TGFP Receptor and the Smad Proteins 

The mechanism of activation of the TGPp receptor is shown schematically in Pig. 

Activation of TGPp is accompanied by multiple phosphorylation on cytoplasmic parts of the receptor this includes Tyr phosphorylation in addition to Ser/Thr phosphorylation. It is assumed that these autophosphorylations occur in trans, i.e., between the protomers of the receptor. Prom the activated TGPp receptor, signals are directed to the transcription level. A set of proteins, known as Smad proteins, are involved in this signal conduction (see Pig. 12 review Heldin et al., 1997, Massague, 1998). Besides Smad proteins, G-proteins and the MAPK cascade are also involved in the downstream signaling of TGPp family members. 

At least nine different Smad proteins have been identified in higher organisms, and 

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Fig. 1. Intracellular events involved in steroid hormone action. A. Model in which the receptor is cytosolic and transfers tothe nucleus after binding with steroid (S). The cytosolic 8S receptor consists of a ligand binding unit ( ) and other units, one of which is a 90 kDa heat shock protein ( ). Activation is shown here as involving dimerisation of the ligand binding unit. This simplification of the true events applies to oestradiol receptor but not necessarily for other receptor classes. There is no agreement as to where activation occurs. B. Model in which unliganded receptor (0) is in the nucleus. A conformational change occurs on binding steroid (S) which may result in increased affinity for specific DNA sequences.

Where specialized fluctuation data are not available, estimates of horizontal spreading can be approximated from convential wind direction traces. A method suggested by Smith (2) and Singer and Smith (10) uses classificahon of the wind direction trace to determine the turbulence characteristics of the atmosphere, which are then used to infer the dispersion. Five turbulence classes are determined from inspection of the analog record of wind direction over a period of 1 h. These classes are defined in Table 19-1. The atmosphere is classified as A, B2, Bj, C, or D. At Brookhaven National Laboratory, where the system was devised, the most unstable category. A, occurs infrequently enough that insufficient information is available to estimate its dispersion parameters. For the other four classes, the equations, coefficients, and exponents for the dispersion parameters are given in Table 19-2, where the source to receptor distance x is in meters. 

Additional tables are furnished for the other stability classes. Note that calms have been distributed among the directions. Such joint frequency data can be used directly in climatological models such as the Climatological Dispersion Model (CDM) (1). The CDM calculates seasonal or annual concentrations at each receptor by considering sources in each wind sector... 

Apart from these two Vertex compounds, only one other caspase inhibitor, BDN-6556, has been used in clinical trials. This compound belongs to the class of oxamyl dipeptides and was originally developed by Idun Pharmaceuticals (taken over by Pfizer). It is the only pan-caspase inhibitor that has been evaluated in humans. BDN-6556 displays inhibitory activity against all tested human caspases. It is also an irreversible, caspase-specific inhibitor that does not inhibit other major classes of proteases, or other enzymes or receptors. The therapeutic potential of BDN-6556 was first evaluated in several animal models of liver disease because numerous publications suggested that apoptosis contributes substantially to the development of some hepatic diseases, such as alcoholic hepatitis, hepatitis B and C (HBV, HCV), non-alcoholic steato-hepatitis (NASH), and ischemia/reperfusion injury associated with liver transplant. Accordingly, BDN-6556 was tested in a phase I study. The drug was safe and... 

Phencyclidine (1 -[1-phenylcyclohexyl]pi peridine HC1 PCP) and its active derivatives produce unique behavioral effects in animals and psychotomimetic effects in humans. Drugs of this class have been demonstrated to bind saturably, reversibly, and with high affinity to specific binding sites in brain (Hampton et al. 1982 Quirion et al. 1981 Sircar and Zukin 1983 Vincent et al. 1979 Zukin and Zukin 1979). These sites have been shown to exhibit a characteristic heterogeneous regional distribution pattern (Quirion et al. 1981 Sircar et al., submitted for publication Zukin and Zukin 1979) distinct from that of any other receptor type. 

In summary, Caco-2 cells studies strongly suggest that carotenoids interact with each other at the level of cellular uptake by the enterocyte. This phenomenon has been explained by the fact that the uptake of several carotenoids involves, at least in part, the same intestinal membrane transporter the scavenger receptor class B type ISR-BI (Reboul et al. 2005, van Bennekum et al. 2005, Moussa et al. 2008). 

The other major class of extracellular LBPs of mammals is the lipocalins (Flower, 1996). These are approximately 20 kDa, P-sheet-rich proteins, performing functions such as the transport of retinol in plasma or milk, the capture of odorants in olfaction, invertebrate coloration, dispersal of pheromones, and solubilizing the lipids in tears (Flower, 1996). The retinol-binding protein (RBP) of human plasma is found in association with a larger protein, transthyretin, the complex being larger than the kidney threshold and thus not excreted, although the RBP itself may dissociate from the complex to interact with cell surface receptors in the delivery of retinol (Papiz et al., 1986 Sundaram et al., 1998). 

Constant Fragment (Fc) This is the stem of the letter Y. It is the part that is identical for all antibodies of the same class for example, all IgGs have the same Fc. The Fc fragment is the part that links the antibody to other receptors and triggers immune response and antigen destruction. 

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