Cell surface receptor interactions

Chan FK-M, Siegel RM, Zacharias D, Swofford R, Holmes KL, et al. 2001. Fluorescence resonance energy transfer analysis of cell surface receptor interactions and signaling using spectral variants of the green fluorescent protein. Cytometry 44 361-368. 

Interesting enough, the laminin al chain (Table 3) carboxyl-terminal globular domain (G Domain) presents multiple biological activities. Recent results showed that biological active regions in the G domain are conserved in the laminin al and a2 chains and play an important role in cell surface receptor interactions [113]. Similar results were obtained with four Drosophila laminin peptides, according to Nomizu et al [114]. 

The ability of bacterial SAgs to activate T cells without using CD4/CD8 as coreceptors opens up the possibility that other cell surface receptors interact... 

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. 

Class 1 and class II MHC molecules bind peptide antigens and present them at the cell surface for interaction with receptors on T cells. The extracellular portion of these molecules consists of a peptide-binding domain formed by two helical regions on top of an eight-stranded antiparallel p sheet, separated from the membrane by two lower domains with immunoglobulin folds. These domains are differently disposed between the two protein subunits in class I and class II molecules. 

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... 

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. 

Etanercept is a fully human dimeric fusion protein composed of human TNF-a p75 receptor fused to the Fc portion of human IgG 1.41 It acts as a tumor necrosis factor-a (TNF-a) inhibitor by binding to and inactivating TNF-a, thus preventing interactions with its cell surface receptors.41 This agent is useful for chronic moderate to severe plaque psoriasis and for psoriatic... 

Neutrophils are the most abundant leukocytes in humans, comprising about two thirds of peripheral blood leukocytes. Upon tissue injury, they rapidly infiltrate injury sites and play an important role in innate immune responses. In addition, they also contribute to the development of adaptive immune responses by producing an array of cytokines and chemokines. Tissue infiltration of neutrophils is initiated by signals generated by the interaction between chemoattractants produced at sites of injury and their corresponding cell surface receptors. Classical chemoattractants, such as C5a, N-formyl-methionyl-leucyl-... 

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). 

Screening the molecular heterogeneity of receptor expression in endothelial cell surfaces is required for the development of vascular-targeted therapies. First, as opposed to targeting purified proteins as discussed above, membrane-bound receptors are more likely to preserve their functional conformation, which can be lost upon purification and immobilization outside the context of intact cells. Moreover, many cell surface receptors require the cell membrane microenvironment to function so that protein-protein interaction may occur. Finally, combinatorial approaches may allow the selection of cell membrane ligands in a functional assay and without any bias about the cellular surface receptor. Therefore, even as yet unidentified receptors may be targeted. 

Interact across a cell membrane Act through a cell surface receptor or intracellularly... 

Table 10.1 Overview of some polypeptide growth factors. Many can be grouped into families on the basis of amino acid sequence homology, or the cell types affected. Most growth factors are produced by more than one cell type and display endocrine, paracrine or autocrine effects on target cells by interacting with specific cell surface receptors...

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