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Multiple Ligands (multiple + ligand)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Growth Hormone Secretagogue Actions On The Pituitary Gland: Multiple Receptors For Multiple Ligands?

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2000
Chen Chen
SUMMARY 1. Growth hormone (GH) secretion is thought to occur under the reciprocal regulation of two hypothalamic hormones, namely GH-releasing hormone (GHRH) and somatostatin (SRIF), through their engagement with specific cell-surface receptors on the anterior pituitary somatotropes. 2. In addition to GHRH and SRIF, synthetic GH-releasing peptides (GHRP) or GH secretagogue(s) (GHS) regulate GH release through the activation of a novel receptor, the GHS receptor (GHS-R). 3. The cloning of the GHS-R from human, swine and rat identifies a novel G-protein-coupled receptor involved in the control of GH secretion and supports the existence of an undiscovered hormone that may activate this receptor. 4. Varieties of intracellular signalling systems are suggested to mediate the action of GHS, which include changes in intracellular free Ca2+ ([Ca2+]i), cAMP, protein kinases A and C, phospholipase C etc. 5. With regard to the use of signalling systems by GHS, especially a new form of GHRP or GHRP-2, a clear species difference has been demonstrated, supporting the possibility of more than one type of GHS-R. [source]

Reticulocyte binding protein homologues are key adhesins during erythrocyte invasion by Plasmodium falciparum

CELLULAR MICROBIOLOGY, Issue 11 2009
Tony Triglia
Summary The Apicomplexan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invades human erythrocytes through multiple ligand,receptor interactions. The P. falciparum reticulocyte-binding protein homologue (PfRh or PfRBL) family have been implicated in the invasion process but their exact role is unknown. PfRh1 and PfRh4, members of this protein family, bind to red blood cells and function in merozoite invasion during which they undergo a series of proteolytic cleavage events before and during entry into the host cell. The ectodomain of PfRh1 and PfRh4 are processed to produce fragments consistent with cleavage in the transmembrane domain and released into the supernatant, at about the time of invasion, in a manner consistent with rhomboid protease cleavage. Processing of both PfRh1 and PfRh4, and by extrapolation all membrane-bound members of this protein family, is important for function and release of these proteins on the merozoite surface and they along with EBA-175 are important components of the tight junction, the transient structure that links the erythrocyte via receptor,ligand interactions to the actin,myosin motor in the invading merozoite. [source]

The lectin-like domain of thrombomodulin interferes with complement activation and protects against arthritis

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2006
M. VAN DE WOUWER
Summary.,Background: Thrombomodulin (TM) is predominantly a vascular endothelial cell plasma membrane glycoprotein that, via distinct structural domains, interacts with multiple ligands, thereby modulating coagulation, fibrinolysis, complement activation, inflammation and cell proliferation. We previously reported that by mediating signals that interfere with mitogen-activated protein kinase and nuclear factor ,B pathways, the amino-terminal C-type lectin-like domain of TM has direct anti-inflammatory properties. Methods: In the current study, we use murine models of acute inflammatory arthritis and biochemical approaches to assess the mechanism by which the lectin-like domain of TM modifies disease progression. Results: Mice lacking the lectin-like domain of TM (TMLeD/LeDmice) develop inflammatory arthritis that is more rapid in onset and more severe than that developed in their wildtype counterparts. In two models of arthritis, treatment of mice with recombinant soluble lectin-like domain of TM significantly suppresses clinical evidence of disease and diminishes monocyte/macrophage infiltration into the synovium, with weaker expression of the pro-inflammatory high mobility group box chromosomal protein 1. While thrombin-TM mediated activation of thrombin activatable fibrinolysis inhibitor inactivates complement factors C3a and C5a, we show that TM has a second independent mechanism to regulate complement: the lectin-like domain of TM directly interferes with complement activation via the classical and lectin pathways. Conclusions: These data extend previous insights into the mechanisms by which TM modulates innate immunity, and highlight its potential as a therapeutic target for inflammatory diseases. [source]

Multiple diverse ligands binding at a single protein site: A matter of pre-existing populations

PROTEIN SCIENCE, Issue 2 2002
Buyong Ma
Abstract Here, we comment on the steadily increasing body of data showing that proteins with specificity actually bind ligands of diverse shapes, sizes, and composition. Such a phenomenon is not surprising when one considers that binding is a dynamic process with populations in equilibrium and that the shape of the binding site is strongly influenced by the molecular partner. It derives implicitly from the concept of populations. All proteins, specific and nonspecific, exist in ensembles of substates. If the library of ligands in solution is large enough, favorably matching ligands with altered shapes and sizes can be expected to bind, with a redistribution of the protein populations. Point mutations at spatially distant sites may exert large conformational rearrangements and hinge effects, consistent with mutations away from the binding site leading to population shifts and (cross-)drug resistance. A similar effect is observed in protein superfamilies, in which different sequences with similar topologies display similar large-scale dynamic motions. The hinges are frequently at analogous sites, yet with different substrate specificity. Similar topologies yield similar conformational isomers, although with different distributions of population times, owing to the change in the conditions, that is, the change in the sequences. In turn, different distributions relate to binding of different sizes and shapes. Hence, the binding site shape and size are defined by the ligand. They are not independent entities of fixed proportions and cannot be analyzed independently of the binding partner. Such a proposition derives from viewing proteins as dynamic distributions, presenting to the incoming ligands a range of binding site shapes. It illustrates how presumably specific binding molecules can bind multiple ligands. In terms of drug design, the ability of a single receptor to recognize many dissimilar ligands shows the need to consider more diverse molecules. It provides a rationale for higher affinity inhibitors that are not derived from substrates at their transition states and indicates flexible docking schemes. [source]