Surface receptor

The ion channel/transporter group is represented by several receptors associated with the long QT syndrome, and the sulfonylurea receptor that is 

The frequencies of each polymorphism are the same for normal adults and asthmatics, so that these primary variations in the structure of the receptor are not considered a major cause of asthma (138). However, the Glyl6 form of the receptor undergoes agonist-promoted downregulation while Glu27 displays resistance to such downregulation. Additionally, 

Receptors with lie at position 164 exhibit sustained, markedly dysfunctional properties with altered high affinity binding and decreased coupling to the stimulatory G protein in transfected cells (31,137), but the rarity of this polymorphism has so far precluded its study in the homozygous state or in situations of clinical interest. 

Drysdale s recent study, the first of its kind, assessed the effect of combinations of SNPs (haplotypes) on response to the drug, albuterol (146). Variation in 13 SNPs could be organized into 12 haplotypes, and investigation of these haplotypes in several discrete populations (Caucasian, African-American, Asian, and Hispanic-Latino) revealed 20-fold differences among the frequencies of the four major haplotypes. Mean responses to bronchodilator therapy with albuterol of individuals with the five most common (FAR haplotypes varied by greater than twofold, but were unrelated to individual SNPs. 

Initial characterization of HIV-1 revealed the presence of the (3-chemokine receptor, CCR5 (also designated CC-CKR-5 and CKR5) was required on the surface of mature human helper T lymphocytes for attachment and 

Many hormones, such as the hormonal amines and all pep-tidic hormones, are unable to penetrate the lipid matrix of the cell membrane, and thus depend on the presence of receptor sites at the surface of target cells. As listed in Table 30-4, there are several types of cell membrane receptors for these hormones, each of which is coupled to a distinct set of intracellular postreceptor pathways. The surface receptors all initiate postreceptor events that involve the phosphorylation of one or more intracellular proteins, some of which are enzymes whose activities depend on the state of phosphorylation. In two of these cases, an intracellular second messenger is utilized to implement the hormonal action and involves G-protein-coupled receptors. One is coupled to the adenylate cyclase-cAMP system and the other is associated with the phosphatidylinositol-Ca + pathway (IP3 pathway). 

Heparan sulfates have been shown to be a component of amyloid plaques in prion diseases (Gabizon et al, 1993). Recently, it has been demonstrated that the addition of heparin competes with the binding of 

Recently, a signal transduction activity of the prion protein by achieving tyrosine kinase Fyn was described (Mouillet-Richard et al, 2000). Since PrpC locates GPI-anchored at the cell surface, whereas Fyn-kinase is associated with the inner plasma membrane of the cell, a transmembrane receptor might mediate the PrP dependent activation of the Fyn-kinase. 

According to Martins et al, in the normal cell PrP and receptors from the same cell or from different cells can interact and mediate signal transduction, triggering their physiological function. They postu- 

PrP Binding Protein cDNA Identified Known Homology Surface Protein Method of Identification Reference 

Pli45 Yes GFAP No ligand blot Oesch etal, 1990 

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P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

Food vitamin B 2 appears to bind to a saUvary transport protein referred to as the R-protein, R-binder, or haptocorrin. In the stomach, R-protein and the intrinsic factor competitively bind the vitamin. Release from the R-protein occurs in the small intestine by the action of pancreatic proteases, leading to specific binding to the intrinsic factor. The resultant complex is transported to the ileum where it is bound to a cell surface receptor and enters the intestinal cell. The vitamin is then freed from the intrinsic factor and bound to transcobalamin II in the enterocyte. The resulting complex enters the portal circulation. 

Transport. Transcobalamin II dehvers the absorbed vitamin 3 2 to cells and is the primary plasma vitamin B22-binding transport protein. It is found in plasma, spinal fluid, semen, and extracellular fluid. Many cells, including the bone marrow, reticulocytes, and the placenta, contain surface receptor sites for the transcobalamin II—cobalamin complex. 

Tissue Uptake and Storage. Cell surface receptors take up the transcobalamin II—cobalamin complex, which is internalized into endosomes. The complex is dissociated and the transcobalamin II released. The mechanism by which cobalamin leaves the endosome is uncertain. 

Many cell-surface receptors contain immunoglobulin-like domains. 

Limbird, L. E. (1995). Cell surface receptors A short course on theory and methods. Martinns Nihjoff, Boston. 

Heldin, C. H. (1995). Dimerization of cell surface receptors in signal transduction. Cell 80 213-223. 

Downregnlation, the reduction in the number of biological targets (e.g., cell surface receptors, enzymes) usually... 

VEGF-Trap is a protein-based product candidate designed to bind all forms of VEGF and the related P1GF, and prevents their interaction with cell surface receptors. VEGF Trap is being pursued in phase II... 

The steroid hormone 1,25-dihydroxy vitamin D3 (calcitriol) slowly increases both intestinal calcium absorption and bone resorption, and is also stimulated through low calcium levels. In contrast, calcitonin rapidly inhibits osteoclast activity and thus decreases serum calcium levels. Calcitonin is secreted by the clear cells of the thyroid and inhibits osteoclast activity by increasing the intracellular cyclic AMP content via binding to a specific cell surface receptor, thus causing a contraction of the resorbing cell membrane. The biological relevance of calcitonin in human calcium homeostasis is not well established. 

Caveolae are invaginations of the plasma membrane. They contain the protein caveolin and are rich in certain phospholipids. Similar to coated pits, they bud off internally forming endocytic vesicles. Caveolae play an important role in the internalization of certain cell surface receptors. 

A process in which a substance gains entry into a cell. Endocytic mechanisms are crucial for a variety of cellular functions such as the uptake of nutrients, regulation of cell surface expression of receptors, maintenance of cell polarity, and more. Receptor-mediated endocytosis via clathrin-coated pits is the most studied endocytic process, which is important for regulation of the time and magnitude of signals generated by a variety of cell-surface receptors. 

Muscarinic acetylcholine receptors (mAChRs) form a class of cell surface receptors that are activated upon binding of the neurotransmitter, acetylcholine. Structurally and functionally, mAChRs are prototypical members of the superfamily of G protein-coupled receptors. Following acetylcholine binding, the activated mAChRs interact with distinct classes of heterotrimeric G proteins resulting in the activation or inhibition of distinct downstream signaling cascades. 

The neurotransmitter acetylcholine (ACh) exerts its diverse pharmacological actions via binding to and subsequent activation of two general classes of cell surface receptors, the nicotinic and the mAChRs. These two classes of ACh receptors have distinct structural and functional properties. The nicotinic receptors,... 

The role of NFAT in the immune system is not restricted to T cells. NFAT proteins are also expressed in other cells of the immune system, such as B cells, NK cells, and mast cells, where they have been shown to regulate the expression of cytokines, cell surface receptors, and immunoglobulins [4, 5]. 

A purinoceptor is a cell surface receptor for the purinergic nucleotides ATP and ADP and for the purine nucleotide, adenosine. 

Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin-like cell surface receptor superfamily inter-acting with several SI00 proteins. 

Hofmann MA, Drury S, Fu C et al (1999) RAGE mediates a novel proinflammatory axis a central cell surface receptor for SlOO/calgranulin polypeptides. Cell 97 889-901... 

The T cell receptor is a clonotypic, T cell specific surface receptor that mostly recognizes peptides bound to MHC molecules on antigen-presenting cells. 

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