Candidate Receptors

The two platelet membrane glycoproteins for which the strongest evidence exists at the present time that they are thrombin receptors are a specific form of the GPIb-DC-V conq lex and PARI, the protease-activated thrombin receptor these will be discussed next in this review. Based on their apparent ability to form complexes with a hrombin, several other proteins had previously t en proposed as thrombin receptors but in only a few cases were the necessary further studies carried out to test these hypotheses. Protease nexin 1 was proposed as a thrombin receptor based on the similar time courses of complex formation and platelet activation but it was subsequently found that protease nexin 1 cannot be a receptor since it is an internal conq onent of platelets that is expressed on the surface only ater activation. Glycoprotein V has also been proposed as a thrombin receptor based on the feet that it can be cleaved by low concentrations of a-thrombin but subsequent studies (reviewed in ) showed that there was no consistent relationship between the rate or extent of GPV hydrolysis and the extent of platelet activation induced by a-thrombin. Another thrombin-activatable receptor, PAW, has been identified in mouse platelets but not in human platelets using a reverse transcriptase/ polymerase chain reaction approach (unpublished data and S.Coughlin, personal communication). PAR3 has, however, been reported cloned from a human platelet cDNA library.  

Despite the extensive binding and functional evidence in the literature for the existence of two different types of thrombin receptors, PARI was initially termed the thrombin receptor and it was asserted that it alone was both necessary and sufficient to explain all 

Whether the tethered ligand peptide alone can induce fibroblast mitogenesis has not so fiir been satisfectorily resolved PARI-related peptides have been reported to be unable to induce mitogenesis in CCL39 hamster fibroblasts in the absence of added growth fectors possessing tyrosine kinase activity in some studies but not in others.  

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Kitagawa, M. et al. Molecular genetic identification of a candidate receptor gene for sweet taste. Biochem. Biophys. Res. Commun. 283 236-242, 2001. 

Scarselli E., Ansuini H., Cerino R., Roccasecca R. M., Acali S., Filocamo G., Traboni C., Nicosia A., Cortese R. and Vitelli A. (2002) The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J. 21, 5017-5025. 

Kitagawa M, Kusakabe Y, Miura H, Ninomiya Y, Hino A (2001) Molecular genetic identification of a candidate receptor gene for sweet taste. Biochem Biophys Res Commun 283 236-242 Lane RP, Young J, Newman T, Trask BJ (2004) Species specificity in rodent pheromone receptor repertoires. Genome Res 14 603-608... 

It has not been examined in detail whether the zebrafish TAARs are expressed in OSNs as chemosensory receptors. Nevertheless, TAARs are likely candidate receptors for polyamines that activate fish OSNs through a unique signaling pathway (Michel et al. 2003 Rolen et al. 2003). 

The role of bioreceptor can be also played by viruses covalently attached to the electrode surface, which was shown for resistance detection of antibody and prostate-specific membrane antigen.135 Taking into account up to 1020 unique species, phage-displayed libraries provide a vast pool of candidate receptors to practically any analyte, including small molecules, proteins and nucleic acids. Piezoelectric virus sensor has been developed e.g. for detection of distinctive antigens of the human cytomegalovirus.136... 

White, S. J., Simmonds, R. E., Lane, D. A., Baker, A. H. (2005). Efficient isolation of peptide ligands for the endothelial cell protein C receptor (EPCR) using candidate receptor phage display biopanning. Peptides, 26, 1264-1269. 

Binding of PrP-AP to cultured cells was significantly reduced in the presence of the calcium chelator EDTA, indicating that for optimum binding, the presence of divalent cations such as Ca might he required. Binding of mouse, human, and hovine cellular PrP as well as PrpSc fj-om BSE-affected brain to the candidate receptor was observed (Cashman etal, 1999). 

Another candidate receptor for signal transduction through the cADPR pathway is the 5-HT2A receptor in tracheal smooth muscle. Here 5-HT in the absence of extracellular Ca + can mobilize Ca + without increasing IP3 formation, an effect that is blocked by prior incubation with ryanodine (Watts etal., 1994). It will be interesting to see if cADPR plays a role in transducing the effects of these two receptor types linked to the contractile processes in smooth muscle. 

Immunohistochemical localization of the avian progesterone receptor and its candidate receptor binding factor (RBF-1). ]. Cell. Biochem., 53, 383-93. 

The evidence for the role of Toll-like receptors 4 or 2 as receptors for OxPLs is based on impaired responses to OxPLs or mmLDL in knockout animal models or after knockdown of TLRs in cultured cells [49-54], OxPLs do not demonstrate canonical activation of TLRs in cells naturally expressing these receptors or in reporter cell lines [55-57]. It can be hypothesized that this discrepancy is explained by the need of additional soluble or membrane-associated proteins that present OxPLs to TLRs [51,52]. The role of TLRs as candidate receptors mediating proinflammatory action of OxPLs is discussed in more detail in Chapter 11 in this book. 

Immobilized GAs appear to interact with GA-receptors at the surface of aleurone protoplasts and induce a-amylase. We have used GA4-Sepharose and Sepharose 6B in affinity chromatography experiments with aleurone extracts and with solubilized aleurone membrane proteins. Unfortunately, many aleurone proteins bind to GA4-Sepharose and Sepharose 6B. Ligand specific elution of proteins has been difficult to demonstrate by analyzing column fractions by SDS-PAGE. The anti-idiotypic antisera 455 1 and 455 2 may provide a more realistic means of assaying column eluates for candidate receptors. 

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