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Results for “Receptor Aggregation”

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At least 1,477 records · Page 82Linked to original sources
PubMed1996

Fas (CD95) expression and death-mediating function are induced by CD4 cross-linking on CD4+ T cells.

The CD4 receptor contributes to T-cell activation by coligating major histocompatibility complex class II on antigen presenting cells with the T-cell receptor (TCR)/CD3 complex, and triggering a cascade of signaling events including tyrosine phosphorylation of intracellular proteins. Paradoxically, CD3 cross-linking prior to TCR stimulation results in apoptotic cell death, as does injection of anti-CD4 antibodies in vivo of CD4 ligation by HIV glycoprotein (gp) 120. In this report we investigate the mechanism by which CD4 cross-linking induces cell death. We have found that CD4 cross-linking results in a small but rapid increase in levels of cell surface Fas, a member of the tumor necrosis factor receptor family implicated in apoptotic death and maintenance of immune homeostasis. Importantly, CD4 cross-linking triggered the ability of Fas to function as a death molecule. Subsequent to CD4 cross-linking, CD4+ splenocytes cultured overnight became sensitive to Fas-mediated death. Death was Fas-dependent, as demonstrated by cell survival in the absence of plate-bound anti-Fas antibody, and by the lack of CD4-induced death in cells from Fas-defective lymphoproliferative (lpr) mice. We demonstrate here that CD4 regulates the ability of Fas to induce cell death in Cd4+ T cells.

Animals↗
PubMed2001

Visualization of Syk-antigen receptor interactions using green fluorescent protein: differential roles for Syk and Lyn in the regulation of receptor capping and internalization.

The cross-linking of the B cell Ag receptor (BCR) is coupled to the stimulation of multiple intracellular signal transduction cascades via receptor-associated, protein tyrosine kinases of both the Src and Syk families. To monitor changes in the subcellular distribution of Syk in B cells responding to BCR cross-linking, we expressed in Syk-deficient DT40 B cells a fusion protein consisting of Syk coupled to green fluorescent protein. Treatment of these cells with anti-IgM Abs leads to the recruitment of the kinase from cytoplasmic and nuclear compartments to the site of the cross-linked receptor at the plasma membrane. The Syk-receptor complexes aggregate into membrane patches that redistribute to form a cap at one pole of the cell. Syk is not demonstrably associated with the internalized receptor. Catalytically active Syk promotes and stabilizes the formation of tightly capped BCR complexes at the plasma membrane. Lyn is not required for the recruitment of Syk to the cross-linked receptor, but is required for the internalization of the clustered BCR complexes. In the absence of Lyn, receptor-Syk complexes at the plasma membrane are long lived, and the receptor-mediated activation of the NF-AT transcription factor is enhanced. Thus, Lyn appears to function to negatively regulate aspects of BCR-dependent signaling by stimulating receptor internalization and down-regulation.

Animals↗
PubMed1990

TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen.

A murine mAb, 5A6 (IgG1), has been isolated by immunization with a human B lymphoma cell line and screening for growth inhibition. The antibody immunoprecipitated a single chain protein of 26 kDa from cell lysates made with Triton X-100 but additional proteins were precipitated when cell lysates were made with the milder detergent CHAPS (3-[3-cholamidopropyl)dimethylammonio)-1-propane sulfate). We have identified one of these coprecipitated molecules as the 16-kDa Leu-13 Ag. 5A6 and anti-Leu-13 showed similar, although not identical, reactivity, growth inhibition and temperature-dependent aggregation effects among hematolymphoid cell lines. The aggregation induced by 5A6 and anti-Leu-13 was not dependent on LFA-1 (lymphocyte function-associated Ag-1). The cell-surface expression of both TAPA-1 (target of an antiproliferative antibody-1) and Leu-13 could be down-modulated by binding to their respective antibodies and they could be reciprocally comodulated. These results suggest that TAPA-1 and Leu-13 form a complex on the cell surface and play a role in growth control through a common pathway.

Antibodies, Monoclonal↗
PubMed1990

Octimibate inhibition of platelet aggregation: stimulation of adenylate cyclase through prostacyclin receptor activation.

Octimibate inhibited ADP- and collagen-induced platelet aggregation in human, rabbit and rat platelet-rich plasma. Washed human platelets treated with octimibate had elevated cyclic AMP (cAMP) levels and cAMP-dependent protein kinase activity. When whole platelets were incubated with radiolabeled phosphate, octimibate produced an increase in the phosphorylation of platelet proteins with relative molecular weights of 22, 26, 50 and 80 kilodaltons. This pattern of protein phosphorylation is identical to that observed when the platelets were treated with forskolin, phosphodiesterase inhibitors or other compounds that elevate platelet cAMP levels. Octimibate also inhibited the rise in intracellular Ca++ caused by thrombin, as measured using Fura-2-loaded platelets, which is consistent with octimibate's ability to elevate platelet cAMP levels. When isolated platelet plasma membranes were treated with octimibate, adenylate cyclase activity was stimulated, reaching maximal activation at 1 microM octimibate. (The maximal activation of adenylate cyclase observed with octimibate is 70-75% of that observed with 10 microM PGE1.) This stimulation of platelet adenylate cyclase activity was enhanced by GTP. Octimibate competed for radiolabeled prostaglandin E1 and lloprost binding to isolated platelet membranes at submicromolar concentrations, but did not compete with radiolabeled prostaglandin D2 binding. These studies suggest that octimibate inhibits platelet aggregation by activating platelet adenylate cyclase through stimulation of platelet prostacyclin receptors.

Adenylyl Cyclases↗
PubMed1982

Potentiation by dazoxiben, a thromboxane synthetase inhibitor, of platelet aggregation inhibitory activity of a thromboxane receptor antagonist and of prostacyclin.

Dazoxiben, a thromboxane (Tx)-synthetase inhibitor, completely prevented platelet TxB2 synthesis, but not the platelet aggregation induced by arachidonic acid (AA) or ADP. It was also ineffective against platelet aggregation brought about by a prostaglandin (PG) endoperoxide analogue, which does not trigger platelet TxA2 synthesis. The association of dazoxiben with a Tx receptor antagonist or with PGI2 resulted in marked potentiation of the latter compounds as inhibitors of platelet aggregation induced by AA or ADP (second wave), but not by U-46619 (a stable analogue of prostaglandin endoperoxides). It therefore appears that inhibition of Tx synthesis does not modify the platelet response to aggregating stimuli but renders platelets more susceptible to inhibition induced by other compounds.

Arachidonic Acids↗
PubMed1995

Tyrosine phosphorylation and synapse formation at the neuromuscular junction.

Protein tyrosine phosphorylation is prevalent throughout the nervous system. It has been implicated to play an important role in the development and maintenance of neuronal functions. In the past few years significant advances have been made in our understanding of the molecular mechanisms of synapse formation and synaptic plasticity. Protein tyrosine phosphorylation appears to be important in the neuron-induced synthesis of the nicotinic acetylcholine receptor and aggregation of synaptic proteins at the neuromuscular junction during development. In addition, protein tyrosine phosphorylation may regulate the ion channel activity of the nicotinic acetylcholine receptor.

Animals↗
PubMed1991

Lateral diffusion of PDGF beta-receptors in human fibroblasts.

When platelet-derived growth factor (PDGF) binds to its receptors a number of biochemical reactions are elicited in the cell. Several models have been presented for the effects of ligand-induced receptor conformation and aggregation on signal transduction but little is known about the direct effects on receptor diffusion. This study concerns the lateral mobility of PDGF receptors in fibroblasts. It was assessed with fluorescence recovery after photobleaching (FRAP), using rhodaminated receptor antibodies or Fab-fragments of the antibody as ligands. The aims of the investigation were: (a) to compare the lateral mobility of membrane receptors of human fibroblasts labelled with either antibodies against the PDGF receptor or Fab-fragments of the same antibodies, and (b) to study the effects of serum or PDGF on the mobility of the receptors. Human foreskin fibroblasts (AG 1523) were grown on coverslips either under standard or under serum-free conditions yielding "normal" and "starved" cells, respectively. Two parameters of the diffusion were evaluated; the diffusion coefficient (D) and the mobile fraction (R) of the receptors. We found that normal fibroblasts had a smaller diffusion coefficient and a lower mobile fraction compared to starved cells using antibodies for receptor labelling. The addition of PDGF, just before the measurement, increased the D and R for normal cells, while starved cells, showing higher initial values, displayed slightly reduced values of D and R. After the addition of serum, D increased and R remained low for normal cells, whereas for starved cells both D and R increased to upper limits of 11.0 x 10(-10) cm2s-1 and greater than 90% respectively. In general, the D and R values, both in normal and starved cells, were higher for cells labelled with Fab-fragments than for antibody-labelled cells. The results are discussed in relation to the natural complexity of the receptor, and how PDGF, serum, antibodies and Fab-fragments might interfere with receptor structure, aggregation state and membrane diffusion characteristics.

Cell Line↗
PubMed1999

Oligonucleotide aggregates bind to the macrophage scavenger receptor.

We have prepared a model receptor containing a Lys cluster (320-340) in the collagen-like domain of the bovine macrophage scavenger receptor, and have shown that it has a similar binding specificity to the native scavenger receptor. The native scavenger receptor is reported to bind the quadruplex structure of nucleotides. In this study, we analyzed the model receptor binding of nucleotides with various structures, random, parallel or antiparallel quadruplex and aggregate forms. This was carried out by direct binding assays using labeled oligonucleotides or surface plasmon resonance, and by an inhibition assay using Chinese hamster ovary (CHO) cells expressing the scavenger receptor. The results showed that the nucleotides forming the quadruplex structure did not exhibit any binding. Only the aggregate forms of the nucleotide could bind to the model receptor. They also inhibited the degradation of acetylated low density lipoprotein by CHO cells expressing the native scavenger receptor, whereas nucleotides that did not bind to the model receptor had no effect on cellular acetylated low density lipoprotein degradation. Our results suggest that the quadruplex structure is not essential but may be required for the formation of the nucleotide aggregates, which can interact with the scavenger receptor.

Amino Acid Sequence↗
PubMed1990

Temperature-dependent lateral and transverse distribution of the epidermal growth factor receptor in A431 plasma membranes.

To elucidate further the structure and molecular dynamics of the epidermal growth factor receptor, temperature-dependent aggregation and extracellular protrusion of the epidermal growth factor receptor in isolated plasma membranes from A431 cells were examined by fluorescence energy-transfer techniques. Epidermal growth factor was labeled at the amino terminus with either fluorescein isothiocyanate or tetramethylrhodamine isothiocyanate. A radionuclide receptor displacement assay demonstrated the bioactivity of these derivatives. Aggregation of the epidermal growth factor receptor was measured by determining the increase in fluorescence energy transfer between receptor-bound fluorescein and tetramethylrhodamine-labeled epidermal growth factor. Energy transfer between receptor-bound fluorescent derivatives was reversibly greater at 37 than 4 degrees C, indicating temperature-dependent aggregation of the receptor. The extracellular protrusion of the epidermal growth factor receptor was calculated from the magnitude of energy transfer between receptor-bound fluorescein labeled epidermal growth factor and 5-(N-dodecanoylamino)-eosin partitioned into the lipid membrane at 4 and 37 degrees C. No significant change in the distance of closest approach between the N-terminus of epidermal growth factor and the plasma membrane was observed at 4 degrees C (69 +/- 2 A) and 37 degrees C (67 +/- 2 A). Thus, the extracellular protrusion of the occupied epidermal growth factor receptor did not change detectably upon receptor aggregation.

Animals↗
PubMed1976

Cell surface control in Blepharisma intermedium (Protozoa Ciliata). Blocking of gamone II-induced homotypic interacting ligands.

PHA, Con-A, or anti-tubulin antibodies inhibit homotypic pair formation, in B, intermedium mating type-I cells in the presence of suboptimal concentrations of gamone II. The inhibition is dependent on the dose of gamone added; the structural conformation and the relative concentration of the inhibitor; and the time of addition of the inhibitor. The block can be selectively prevented by competitive inhibitors of each ligand. The receptors for the inhibitors are distinctive and there is no cross-reaction between the ligands. It is concluded that ligand binding and subsequent receptor-ligand aggregation must induce a change within the cell-surface membrane, which distorts the distribution and/or affects an optimal conformational aspect of a specific membrane-receptor system for the gamon, a prerequisite for cell pair formation.

Acetylgalactosamine↗
PubMed1982

Heterogeneity of human lymphocyte Fc receptors: studies using heat-aggregated and antigen-complexed IgG from human, rabbit, guinea pig, horse and goat.

We have studied the ability of human peripheral blood lymphocytes (HuPBL)4 to interact with IgG from several animal species. Three functions or activities that are reported to depend on an interaction between complexed IgG and HuPBL receptors (R) for the Fc piece of IgG (Fc gamma R) were compared: (1) antibody-dependent cell-mediated cytotoxicity (ADCC); (2) binding of heat-aggregated IgG (aggG); and (3) rosette formation with IgG-sensitized erythrocytes [RBC-A(gamma)]. IgG (and IgM) antibodies to chicken erythrocytes (CRBC) were purified from the sera of the following species after injection with CRBC stroma: (1) horse (Ho); (2) goat (Go); (3) rabbit (Ra); and (4) guinea pig (Gp). Good IgG-agglutinating antibody titers were obtained from each injected species. Using 51Cr-labeled CRBC targets and HuPBL effector cells, only Ra anti-CRBC IgG gave good ADCC at high dilutions. Ho and Go anti-CRBC (IgG) failed to give ADCC, and Gp anti-CRBC (IgG) gave approx. 30% of the level of kill as Ra. Ra Fab2 fragments of IgG antibody failed to produce ADCC. Treatment of HuPBL with Ra anti-lymphocyte serum (ALS) almost totally ablated ADCC, whereas HoALS failed to alter ADCC. Pretreatment of HuPBL with aggG showed that Ra or Hu aggG gave essentially equal inhibition of ADCC, Gp gave approx. 30% of the degree of inhibition as Hu and Ra, and Ho or Go aggG had essentially no effect of ADCC. These results confirmed the following order of ability of IgG to interact with HuPBL ADCC killer (K) cells: (Hu greater than or equal to)Ra greater than Gp much greater than Ho, Go. The data suggest that Gp IgG interacts with only a subpopulation (approximately 30%) of HuPBL K cells. The binding of aggG to total HuPBL failed to strictly correlate with the ADCC results or with the results of rosette formation between total HuPBL and CRBC-A(gamma). The observations suggest that there is a heterogeneity of Fc gamma R between K and non-K cell subpopulations of HuPBL both in terms of the type of complexed IgG they are able to bind, and in terms of species of origin of the IgG. The data also support contentions that Fc gamma R that bind RBC-A (gamma) complexes differ from those that bind aggG.

Animals↗