Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Receptor Aggregation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1983

Electron microscopic localization of receptors for aggregated beta 2-microglobulin on the surface of beta-hemolytic streptococci.

The presence and location of receptors for aggregated human beta 2-microglobulin (beta 2m) on the surface of group A, C, and G streptococci were studied by electron microscopic techniques. Ferritin-conjugated aggregates of human beta 2m were used in direct binding experiments. Ferritin-conjugated antibodies against beta 2m were employed in a two-step indirect binding assay where the streptococci were incubated with unlabeled beta 2m aggregates before the addition of antibodies. Similar results were obtained with these two methods. Among tested group C and G strains, some showed binding of beta 2m, whereas others were negative. In group A streptococci, beta 2m binding was localized to filamentous structures typical of M protein. In two M protein-negative group A strains, the reactivity was heterogeneous, revealing a majority of unlabeled, but also some heavily labeled streptococci. Morphologically, these beta 2m-binding bacteria exhibited M protein-like projections in contrast to the smooth surfaces of unlabeled cells.

Cell Membrane↗
PubMed1982

Involvement of collagen in the aggregation of acetylcholine receptors on cultured muscle cells.

The role of collagen macromolecules in the aggregation of acetylcholine receptors on the surface of cultured rat muscle cells was investigated. Both the synthesis and secretion of collagen, as well as acetylcholine receptor aggregation were stimulated by treatment of muscle cultures with an embryonic brain extract. Treatments with cis-hydroxyproline or monensin, which interfere with collagen synthesis and secretion, significantly reduced the number of acetylcholine receptor aggregates detected. Incubation of the cultures with embryonic brain extract induced a decrease in extractability of acetylcholine receptors. This effect could be reversed by treating the cells with bacterial collagenase. In addition, affinity purified antibodies against collagen of types I and IV inhibited the aggregation of acetylcholine receptors by stimulated brain extract. These data suggest that neurotrophic factor(s) present in embryonic nerve tissue have the ability to induce collagen production; the collagen formed plays a role in the formation and/or stabilization of acetylcholine receptor aggregates and possibly also of synaptic connections.

Animals↗
PubMed1985

Properties of the Syrian hamster phosphomannosyl receptor: an aggregate of low molecular weight proteins.

Phosphomannosyl receptor (PMR) isolated from Syrian hamster liver was purified to apparent homogeneity by affinity chromatography and one-dimensional PAGE. On one-dimensional PAGE, the receptor migrated with a Mr approximately equal to 215,000 as detected by a silver-staining reagent or by immunoblotting [utilizing antiPMR generated against purified hamster PMR (Mr 215,000) sequentially purified by affinity chromatography and NaDodSO4/PAGE]. On two-dimensional PAGE the receptor was partially dissociated into low-molecular weight components. The protein distribution on immunoblots of two-dimensional gels of hamster liver homogenates was nearly identical to that observed for purified hamster liver PMR. When liver homogenates were subjected to one-dimensional PAGE and immunoblotted under nonreducing conditions, an intensely labeled band that migrated with an apparent Mr of 43,000-49,000 was observed; under reducing conditions a single band with a Mr of 49,000 was observed. The low molecular weight compound was present in the soluble 130,000 X g supernatant but not in the particulate fraction of liver homogenates. An immunoreactive component of similar molecular weight was also present in hamster serum and plasma. These results suggest that PMR is either an aggregate comprised of small molecular weight components or, alternatively, that a number of small molecular weight components are tightly associated with PMR.

Animals↗
PubMed1984

Characterization and down-regulation of opiate receptors in aggregating fetal rat brain cells.

Aggregating brain cells prepared from embryonic rats bind radioactive opiates in a stereospecific manner. The drug selectivity, receptor content during culturing and down-regulation of these apparent opiate receptors were studied in aggregates prepared from the embryonic hindbrain or forebrain. The receptor content in hindbrain but not forebrain aggregates was increased up to 3-fold after 21 days in culture. Differences between the receptors of the two types of aggregates were also observed in the affinity of opiate alkaloids and D-Ala2,D-Leu5-enkephalin (DADL). The potent opiate alkaloid etorphine induced down-regulation of opiate receptors in aggregates prepared from either brain region whereas DADL was a potent down-regulator in the forebrain but not in the hindbrain aggregates and morphine had no effect in both tissues. The implications of these results concerning the control of various types of opiate receptors in the whole animal are discussed.

Animals↗
PubMed1997

Biochemical evidence that the phosphorylated tyrosines, serines, and threonines on the aggregated high affinity receptor for IgE are in the immunoreceptor tyrosine-based activation motifs.

Activation of cells mediated by the high affinity receptor for IgE leads to rapid phosphorylation of tyrosines (and later other residues) on the receptor's beta and gamma subunits, and there is circumstantial evidence that the tyrosines modified are in the so-called immunoreceptor tyrosine-based activation motifs (ITAMs). We identified and quantitated the residues phosphorylated on the subunits of the native receptor by comparing the properties of peptides derived from the receptors radiolabeled in vivo or in vitro with those of synthetic peptides. Our results with receptors labeled in vivo confirm that only the tyrosines in the ITAMs of beta and gamma became phosphorylated, and preferentially, those in the canonical YXX(L/I) sequences. The extent of phosphorylation of the canonical tyrosines was of the same order of magnitude, but the amino-terminal canonical tyrosine in the ITAM of the beta subunit was consistently phosphorylated to a lesser degree. The non-canonical ITAM tyrosine in the beta subunit was considerably less phosphorylated. Phosphorylation of serine (on beta) and threonine (on gamma) also occurred mainly in the ITAMs, but selectively at some positions whose characteristics seem to be conserved among other receptors containing ITAMs. The studies with receptor complexes isolated and radiolabeled in vitro gave similar results for phosphorylation of tyrosines, suggesting that the latter, much simpler system is a useful model for more detailed studies.

Amino Acid Sequence↗
PubMed1998

Organizing effects of rapsyn on neuronal nicotinic acetylcholine receptors.

Targeting receptors to appropriate locations on the cell surface is a critical task for neurons. We have examined the possibility that rapsyn controls the distribution of nicotinic receptors on neurons as it does nicotinic receptors on muscle fibers. Cotransfection of QT6 cells with rapsyn and neuronal nicotinic receptor cDNA constructs produced receptor aggregates or clusters that codistributed in part with rapsyn protein. Though all nicotinic receptor subtypes tested were affected by rapsyn, receptors containing the alpha 7 gene product were among the most responsive. In addition, rapsyn caused a portion of the nicotinic receptors containing alpha 7 subunits to become resistant to solubilization with nonionic detergent and to display a marked increase in metabolic stability. The results are consistent with rapsyn linking the receptors to cytoskeletal elements and suggest that it may play an organizing role determining the fate and location of nicotinic receptors on neurons.

Animals↗
PubMed1999

C1q-binding proteins and C1q receptors.

Aggregated or immobilized complement C1q induces cellular responses in many different cell types. C1q-induced cellular responses may be involved in host defense and in protection against autoimmunity because C1q-deficient humans have infectious complications and a very high incidence of autoimmune disease. The search for the C1q receptor(s), which has been ongoing for 25 years, has led recently to the recognition that proteins identified as binding to C1q may be divided into two groups: C1q-binding molecules that are normally intracellular; and cell surface C1q receptors.

Carrier Proteins↗
PubMed1981

Effect of temperature on phospholipase C induced alterations in insulin binding.

Regulation of insulin-receptor affinity is at present poorly understood. In this study membrane structure was modified by exposing placental membranes to phospholipase C and the subsequent effect on insulin binding and dissociation was examined. As previously described, when insulin-receptor binding was performed at 4 degrees C, phospholipase C treated membranes showed an increase in the apparent number of insulin receptors. However, when binding was performed at 24 degrees C, the predominant effect of prior phospholipase C treatment was to increase the affinity of binding. At this temperature, phospholipase C pretreatment also increased membrane fluidity. Cytochalasin B, an agent which disrupts receptor aggregates, lowered average affinity at 24 degrees C. Phospholipase C treatment slowed the dissociation rate in 'infinite dilution' at 24 degrees C but the accelerating effect of 100 ng/ml insulin (negative cooperativity) was greatly enhanced. These studies suggest that in addition to its effect in unmasking receptor sites, increased membrane fluidity induced by phospholipase C may cause higher affinity binding by allowing greater receptor or receptor subunit aggregation. Receptor or subunit aggregation within a fluid membrane structure may determine in part the affinity of insulin-receptor binding and the kinetic phenomenon known as negative cooperativity.

Cytochalasin B↗
PubMed2000

Insulin receptor binding kinetics: modeling and simulation studies.

Biological actions of insulin regulate glucose metabolism and other essential physiological functions. Binding of insulin to its cell surface receptor initiates signal transduction pathways that mediate cellular responses. Thus, it is of great interest to understand the mechanisms underlying insulin receptor binding kinetics. Interestingly, negative cooperative interactions are observed at high insulin concentrations while positive cooperativity may be present at low insulin concentrations. Clearly, insulin receptor binding kinetics cannot be simply explained by a classical bimolecular reaction. Mature insulin receptors have a dimeric structure capable of binding two molecules of insulin. The binding affinity of the receptor for the second insulin molecule is significantly lower than for the first bound insulin molecule. In addition, insulin receptor aggregation occurs in response to ligand binding and aggregation may also influence binding kinetics. In this study, we develop a mathematical model for insulin receptor binding kinetics that explicitly represents the divalent nature of the insulin receptor and incorporates receptor aggregation into the kinetic model. Model parameters are based upon published data where available. Computer simulations with our model are capable of reproducing both negative and positive cooperativity at the appropriate insulin concentrations. This model may be a useful tool for helping to understand the mechanisms underlying insulin receptor binding and the coupling of receptor binding to downstream signaling events.

Computer Simulation↗
PubMed1982

Studies on the chicken lymphocyte receptor for aggregated IgG.

Chicken lymphocytes isolated from different lymphoid organs were analyzed for Fc IgG receptor by binding of heat aggregated IgG (agg IgG) in the indirect immunofluorescence test. The binding of agg IgG was shown to be specific for Fc IgG receptor, since IgM and F(ab')2 fractions were bound to the lymphocytes in a much less degree. The highest frequency of agg IgG binding cells, almost 100%, was found in the bursa of Fabricius. In contrast to bursa, only a small percentage of thymus cells bound agg IgG. Dose-dependent experiments showed that binding of agg IgG to thymus cells takes place only at high concentrations of the aggregates whereas bursa cells bind agg IgG also at low concentrations. The finding indicates the existence of high and low avidity agg IgG receptors and/or different density of Fc receptors on bursa and thymus cells. A far lower percentage of EA rosette forming cells than of agg IgG binding cells in the various lymphoid organs may depend on the existence of two different Fc IgG receptors on the chicken lymphocytes.

Animals↗
PubMed1989

Fluorescence correlation spectroscopy for detecting submicroscopic clusters of fluorescent molecules in membranes.

The formation of cell surface receptor clusters has been implicated or confirmed in the mechanism of signal transduction across biological membranes for a variety of processes, including receptor-mediated phagocytosis and endocytosis and cellular response to hormones and neurotransmitters. Fluorescence correlation spectroscopy (FCS) is one technique that may provide insight into the kinetics and extent of receptor aggregation. Recent theoretical and experimental developments in FCS for the investigation of submicroscopic clusters of fluorescent molecules are described and the potential applications of the technique to receptor aggregation are reviewed.

Cell Membrane↗
PubMed1998

Physical and functional association of Fc alpha R with protein tyrosine kinase Lyn.

In this report, we show that the Src family nonreceptor protein tyrosine kinase (PTK) Lyn associates with aggregated IgA Fc receptor (Fc alpha R) in the monocytic cell line THP-1. Receptor aggregation and subsequent immunoprecipitation of receptor complexes with huIgA adsorbed to nitrocellulose particles shows that Lyn associates with Fc alpha R by a mechanism sensitive to short treatment with the Src family-selective inhibitor PP1. However, interaction of Lyn with IgG Fc receptor (Fc gamma R) in THP-1 cells was unaffected by short treatment with the PTK inhibitor. Cross-linking of Fc alpha R induced tyrosine phosphorylation of several cellular proteins, including p72Syk, which appears to be a major target of early PTK activity. Unexpectedly, in vitro kinase assays showed that Fc alpha R aggregation-induced tyrosine phosphorylation of Syk did not result in upregulation of Syk activity. Despite the lack of enhanced Syk kinase activity, downstream signaling after Fc alpha R cross-linking was functional and induced the release of significant amounts of interleukin-1 receptor antagonist and interleukin-8. The induction of cytokine release was completely blocked by PP1, thus confirming the biological significance of the association of Lyn with aggregated Fc alpha R. Our data show that early signal transduction after Fc alpha R cross-linking as well as Fc alpha R-mediated activation of cellular effector functions depends on Src family kinase activity. The Src-family PTK involved in Fc alpha R-mediated tyrosine phosphorylation appears to be Lyn, which coprecipitated with aggregated Fc alpha R complexes.

Cell Line↗
PubMed1984

Altered surface distribution of both C3b receptors and Fc receptors on neutrophils induced by anti-C3b receptor or aggregated IgG.

Human neutrophils to which monospecific Fab' or F(ab')2 anti-C3b receptor had been bound at 0 degrees C were incubated for timed intervals at temperatures ranging from 0 degrees C to 37 degrees C, after which the cells were labeled with TRITC -conjugated second antibody. Neutrophils bearing Fab' anti-C3b receptor and incubated for up to 30 min at 37 degrees C, and cells bearing F(ab')2 anti-C3b receptor and incubated at 0 degrees C, exhibited diffusely distributed punctate clusters of receptors. Neutrophils bearing the bivalent anti-receptor and incubated at 30 degrees C or 37 degrees C for 5 min had redistributed C3b receptors into caps and patches that were associated with subplasmalemmal accumulations of myosin. The redistribution of cross-linked C3b receptors was inhibited by pretreatment of the neutrophils with either cytochalasin D or chlorpromazine. On approximately one-half of the cells demonstrating capped C3b receptors there was a corresponding redistribution of Fc receptors, as demonstrated by subsequent binding of FITC-aggregated IgG (FITC agg-IgG). In contrast, capping of C3b receptors did not alter the diffuse distribution of HLA-A on these cells. Cross-linking of Fc receptors on neutrophils by FITC agg-IgG also induced temperature-dependent capping of these receptors that was inhibited by cytochalasin D and chlorpromazine. In approximately one-half of the cells demonstrating capped Fc receptors, subsequent labeling of C3b receptors revealed a similar redistribution of these receptors. Thus, the neutrophil responds to cross-linking of either C3b receptors or Fc receptors by a cytoskeletal-dependent rearrangement of both receptors that causes their overlapping topographic distribution, demonstrating a form of cooperative interaction between these two types of receptors that are involved in the phagocytic reactions of these cells.

Animals↗
PubMed2007

Peripheral-type benzodiazepine receptor (PBR) aggregation and absence of steroidogenic acute regulatory protein (StAR)/PBR association in the mitochondrial membrane as determined by bioluminescence resonance energy transfer (BRET).

The steroidogenic acute regulatory protein (StAR) is responsible for acute control of cholesterol transport across the mitochondrial membrane, however the mechanism of StAR-associated cholesterol transport is unknown and may involve the peripheral-type benzodiazepine receptor (PBR)/endozepine system. Several molecules of PBR may associate to form a channel through which cholesterol passes to the inner mitochondrial membrane, and endozepine is the natural ligand for PBR. Bioluminescence resonance energy transfer (BRET) was used to test StAR/PBR/endozepine interactions, PBR aggregation, and the effect of second messengers on interactions. There was no evidence of StAR/PBR, StAR/endozepine, or PBR/endozepine interactions. The StAR and PBR fusion proteins were trafficking to the mitochondria as expected, but the endozepine fusion protein was not localized to the mitochondria indicating that it was not biologically active. Data were obtained indicating that PBR forms aggregates in the mitochondrial membrane. Energy transfer between PBR fusion proteins was dose and time dependent, but there was no effect induced by PK11195 ligand binding or pharmacologic activation of PKA or PKC second messenger pathways. It appears that PBR aggregates in the mitochondrial membrane, however there was no evidence that PBR aggregation is regulated in the acute control of steroidogenesis, or that PBR and StAR interact.

Animals↗
PubMed1998

Dimerization of the muscle-specific kinase induces tyrosine phosphorylation of acetylcholine receptors and their aggregation on the surface of myotubes.

During development of the neuromuscular junction, neuronal splice variants of agrin initiate the aggregation of acetylcholine receptors on the myotube surface. The muscle-specific kinase is thought to be part of an agrin receptor complex, although the recombinant protein does not bind agrin with high affinity. To specify its function, we induced phosphorylation and activation of this kinase in the absence of agrin by incubating myotubes with antibodies directed against its N-terminal sequence. Antibody-induced dimerization of the muscle-specific kinase but not treatment with Fab fragments was sufficient to trigger two key events of early postsynaptic development: acetylcholine receptors accumulated into aggregates, and their beta-subunits became phosphorylated on tyrosine residues. Heparin partially inhibited receptor aggregation induced by both agrin and anti-muscle-specific kinase antibodies. In contrast, it did not affect kinase or acetylcholine receptor phosphorylation. These data indicate that agrin induces postsynaptic differentiation by dimerizing the muscle-specific kinase. They also suggest that activation of the kinase domain can account for only part of agrin's effects. Dimerization of this molecule appears to activate an additional signal, most likely by organizing a scaffold for other postsynaptic proteins.

Agrin↗
PubMed1998

Fc epsilonRI-mediated induction of TNF-alpha gene expression in the RBL-2H3 mast cell line: regulation by a novel NF-kappaB-like nuclear binding complex.

Using rat basophilic leukemia (RBL-2H3) cells as a model, we investigated how aggregation of the high affinity receptor for IgE (Fc epsilonRI) regulates TNF-alpha gene expression. Antigenic stimulation of RBL-2H3 cells led to an increase in newly synthesized TNF-alpha mRNA that was dependent on continuous receptor aggregation and did not require de novo protein synthesis. Kinetic analysis showed that maximal levels were achieved at 60 min and waned by 180 min of stimulation. Concomitant with the transcriptional activation of the TNF-alpha gene, the rapid appearance and disappearance of a previously uncharacterized nuclear NF-kappaB DNA binding activity, comprised of two distinct protein complexes, were observed. These protein complexes bound to NF-kappaB sites within the TNF-alpha gene and contained novel proteins (three species of Mr between 90,000-110,000) distinct from the classical proteins in NF-kappaB complexes. The induced NF-kappaB binding activity required continuous receptor stimulation and induced NF-kappaB-dependent reporter gene expression. Consistent with a role for the novel NF-kappaB nuclear binding activity in TNF-alpha gene expression, deletion of several 5' kappaB elements in the TNF-alpha promoter abolished all measurable Fc epsilonRI-dependent induction of a reporter construct. Pharmacologic agents that inhibited the NF-kappaB binding activity also inhibited TNF-alpha mRNA expression. Our results demonstrate that a novel NF-kappaB-like nuclear binding activity plays an important role in regulation of the rapid and transient transcriptional activation of the TNF-alpha gene via Fc epsilonRI.

Animals↗
PubMed1999

Urokinase receptor (CD87) aggregation triggers phosphoinositide hydrolysis and intracellular calcium mobilization in mononuclear phagocytes.

Leukocytes utilize urokinase receptors (uPAR; CD87) in adhesion, migration, and matrix proteolysis. uPAR aggregate at cell-substratum interfaces and at leading edges of migrating cells, so this study was undertaken to determine whether uPAR aggregation is capable of initiating activation signaling. Monocyte-like U937 cells were labeled with fluo-3-acetoxymethyl ester to quantitate intracellular Ca2+ concentrations ([Ca2+]i) by spectrofluorometry, and uPAR was aggregated by mAb cross-linking. uPAR aggregation induced highly reproducible increases in [Ca2+]i of 103.0 +/- 10.9 nM (p < 0.0001) and >3-fold increases in cellular d-myoinositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels. Similar increases in [Ca2+]i were also elicited by uPAR aggregation in human monocytes, but cross-linking a control IgG2a had no effect on [Ca2+]i. Selectively cross-linking uPA-occupied uPAR with an anti-uPA mAb produced smaller increases in [Ca2+]i, but fully saturating uPAR with exogenous uPA enhanced the [Ca2+]i response to equal the effect of aggregating uPAR directly. Increased [Ca2+]i was inhibited by thapsigargin, herbimycin A, and U73122, but only partially reduced by low extracellular [Ca2+], indicating that uPAR aggregation increases [Ca2+]i by activating phospholipase C through a tyrosine kinase-dependent mechanism, generating Ins(1,4,5)P3 and releasing Ca2+ from Ins(1,4, 5)P3-sensitive intracellular stores. Cross-linking the beta2 integrin CR3 could not duplicate the effect of uPAR cross-linking, and uPAR-triggered Ca2+ mobilization was not blocked by anti-CR3 mAbs. These results indicate that uPAR aggregation initiates phosphoinositide hydrolysis by mechanisms that are not strictly dependent on associated uPA or CR3.

Benzoquinones↗
PubMed1978

Aggregation of sponge cells. XIV. Possible substitution of calcium ions by polycations.

Single cells from the siliceous sponge Geodia cydonium, obtained after chemical dissociation, reaggregate in the presence of the aggregation factor in Ca2+-containing medium to large aggregates. It was found that polyvalent organic cations (polylysine, spermine, spermidine, putrescine) enhance the Ca2+-mediated cell aggregation. In Ca2+-free medium these compounds also cause reaggregation; aggregates of a diameter up to 800 micron are formed within 120 min. Proteins, containing basic groups of amino acid residues have no influence on cell aggregation. Monovalent cations inhibit the reaggregation process. The enhancing effect of polyvalent organic cations on cell aggregation is dependent on the presence of the soluble aggregation factor. From the findings that polycations do not alter the duration of the lag phase (a characteristic of the aggregation factor-mediated Geodia cell reaggregation) and act in cooperation with the aggregation receptor, we assume that the polycations bind between the aggregation factor and the aggregation receptor.

Animals↗