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 73 records · Page 4Linked to original sources
PubMed1995

Fc alpha receptors mediate release of tumour necrosis factor-alpha and interleukin-6 by human monocytes following receptor aggregation.

The functional capacity of the human monocyte receptor for the Fc portion of IgA (Fc alpha R) in mediating signal transduction was evaluated by cytokine release. F(ab')2 fragments of anti-Fc alpha R monoclonal antibodies (mAb) were used as specific probes to induce release of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Multivalent cross-linking by a secondary anti-mouse antibody [F(ab')2 fragments] induced a significant release of TNF-alpha and IL-6 by human blood mononuclear cells, indicating requirements for Fc alpha R aggregation on the cell surface to transmit signals. Both cytokines were released exclusively by adherent cells, identifying monocytes as the responding cells within the mononuclear cell population. This cytokine release could not be due to contaminating endotoxins, because it was not abolished by polymyxin B, a lipopolysaccharide (LPS) inhibitor. Moreover, purified recombinant soluble Fc alpha R inhibited the anti-Fc alpha R mAb-mediated cytokine release from blood monocytes, demonstrating that TNF-alpha and IL-6 were released in a receptor-specific manner. Our data suggest that Fc alpha R, through its capacity to mediate secretion of IL-6, may play an important role in B-cell proliferation and immunoglobulin production. On the other hand, release of TNF-alpha following stimulation of Fc alpha R molecules directly implicates these receptors in amplification and regulation of the inflammatory process occurring during IgA-mediated host defence.

Animals↗
PubMed1984

Luteinizing hormone (LH) receptor aggregation: modification of ferritin-LH binding and aggregation by prostaglandin F2 alpha and ferritin-LH.

The interaction of LH and its receptor was investigated by ultrastructural analysis of ferritin-LH (FELH) binding to isolated rat luteal cells in the absence and presence of prostaglandin F2 alpha (PGF2 alpha), an inhibitor of LH-stimulated cAMP production. FELH, with a molar ratio of FE to LH of 1:1, bound specifically to LH receptors, either singly or in small groups (microaggregates), at intervals on luteal cell surfaces. FELH elicited a dose-dependent increase in progesterone production, and its binding increased with increased FELH concentration. The number of LH receptors per cell, estimated from particle counts, was about 6.2 +/- 0.6 X 10(4), similar to estimates from Scatchard analysis of [125I]iodo-hCG binding. Microaggregate size increased in parallel with FELH binding. Only partial aggregation was seen at concentrations of FELH that elicited near-maximal progesterone secretion. Aggregation continued to increase at FELH concentrations beyond that required to elicit maximal progesterone secretion. In the presence of PGF2 alpha, FELH-stimulated progesterone production was attenuated, and FELH binding decreased from 2.9 +/- 0.4 X 10(4) to 2.1 +/- 0.3 X 10(4) receptors/cell. PGF2 alpha did not alter microaggregate size on cells labeled with FELH at 4 C when membrane fluidity was already reduced, but did substantially reduce microaggregate size at 37 C. We conclude that FELH binds initially at random sites on membranes of isolated luteal cells and that as binding increases, receptors aggregate into small groups. Furthermore, microaggregates are related in part to receptor occupancy and possibly also to levels of cAMP or activation of the adenylate cyclase mechanism.

Animals↗
PubMed1998

The putative sponge aggregation receptor. Isolation and characterization of a molecule composed of scavenger receptor cysteine-rich domains and short consensus repeats.

Porifera (sponges) are the oldest extant metazoan phylum. Dissociated sponge cells serve as a classic system to study processes of cell reaggregation. The reaggregation of dissociated cells is mediated by an extracellularly localized aggregation factor (AF), based on heterophilic interactions of the third order; the AF bridges two cells by ligating a cell-surface-bound aggregation receptor (AR). In the present study we report cloning, expression and immunohistochemical localization of a polypeptide from the marine sponge Geodia cydonium, which very likely represents the AR. The presumed AR gene gives rise to at least three forms of alternatively spliced transcripts of 6.5, 4.9 and 3.9 kb, as detected by northern blotting. Two cDNA clones corresponding to the shorter forms were already reported earlier; here we present an analysis of the largest. All three putative polypeptides feature scavenger receptor cysteine-rich (SRCR) domains. The largest form, SRCR-SCR-Car, is a cell-surface receptor of molecular mass 220 kDa, which is assumed to be the cell-adhesion receptor AR; the second form, SRCR-Re, is also a putative receptor of 166 kDa, while the third form, SRCR-Mo, is a soluble molecule of 129 kDa. The SRCR-SCR-Car molecule consists of fourteen SRCR domains, six short consensus repeats (SCRs), a C-terminal transmembrane domain and a cytoplasmic tail; its fourteenth SRCR domain features an Arg-Gly-Asp tripeptide. To obtain monoclonal antibodies, a 170-amino-acid-long polypeptide that is found in all three forms of the SRCR-containing proteins was expressed in E. coli. In a western blot of sponge cells lysate the monoclonal antibody raised against the recombinant polypeptide recognized two major immuno-reacting polypeptides (220 and 117 kDa) and two minor bands (36 and 32 kDa). The antibody was found to react with antigen(s) predominantly localized on the plasma membranes of cells, especially those of spherulous cells. In a functional assay Fab' fragments of the antibodies suppressed AF-mediated cell-cell reaggregation. Additionally, a recombinant SRCR-soluble fragment effectively inhibited AF-mediated cell-cell reaggregation. We conclude that the 220 kDa SRCR-containing protein of the sponge G. cydonium is very likely the AR.

Amino Acid Sequence↗
PubMed2000

Alpha-galactosidase stimulates acetylcholine receptor aggregation in skeletal muscle cells via PNA-binding carbohydrates.

Aggregation of nicotinic acetylcholine receptors (AChRs) in skeletal muscle is an essential step in the formation of the mammalian neuromuscular junction. While proteins that bind to myotube receptors such as agrin and laminin can stimulate AChR aggregation in cultured myotubes, removal of cell surface sialic acids stimulates aggregation in a ligand-independent manner. Here, we show that removal of cell surface alpha-galactosides also stimulates AChR aggregation in the absence of added laminin or agrin. AChR aggregation stimulated by alpha-galactosidase was blocked by peanut agglutinin (PNA), which binds to lactosamine-containing disaccharides, but not by the GalNAc-binding lectin Vicia villosa agglutinin (VVA-B4). AChR aggregation stimulated by alpha-galactosidase potentiated AChR clustering induced by either neural agrin or laminin-1 and could be inhibited by muscle agrin. These data suggest that capping of cell surface lactosamines or N-acetyllactosamines with alpha-galactose affects AChR aggregation much as capping with sialic acids does.

Acetylgalactosamine↗
PubMed1993

Local induction of acetylcholine receptor aggregates on cultured rat myotubes by a partially purified protein from fetal pig brain.

It has been suggested that at the time of innervation, developing neurites release one or more soluble factors that locally induce acetylcholine receptor (AChR) aggregate formation at the synaptic site. To test this hypothesis, we developed a model system that mimics the local, neural induction of AChR aggregation at developing synapses. Partially purified protein derived from fetal pig brain was applied locally to the surface of cultured myotubes via a micropipet. We found that local application of this factor for as little as 30 min induced the formation of AChR aggregates that were restricted to a region within 30 microns around the release site. In addition, the locally applied factor induced a local AChR aggregation response, but did not cause a detectable change in the myotube resting membrane potential at the release site. Our data support a soluble factor hypothesis and suggest that neither cell-cell contact nor local electric fields are necessary for the initial induction of AChR aggregation.

Animals↗
PubMed1993

Protein-tyrosine kinase p72syk in high affinity IgE receptor signaling. Identification as a component of pp72 and association with the receptor gamma chain after receptor aggregation.

Protein-tyrosine phosphorylation plays a critical role in the high-affinity IgE receptor (Fc epsilon RI) signaling. Here we investigated the involvement of the tyrosine kinase p72syk in Fc epsilon RI signaling in the rat mast cell line RBL-2H3. Specific antibodies were raised against peptides synthesized on the basis of the deduced peptide sequence of an essentially full-length rat syk cDNA. The expression of p72syk in RBL-2H3 cells was demonstrated with these antibodies. The aggregation of Fc epsilon RI led to the tyrosine phosphorylation of p72syk that was detected after 15 s of stimulation, reached a plateau by 5 min, and was not induced by calcium influx or protein kinase C activation. Association of p72syk with the tyrosine phosphorylated Fc epsilon RI gamma chain was detected only after receptor aggregation. We previously demonstrated that aggregation of the Fc epsilon RI on mast cells results in the tyrosine phosphorylation of a 72-kDa protein (pp72) involved in IgE signaling. The depletion of p72syk from RBL-2H3 cell lysates resulted in only a slight decrease in the amount of pp72. These results demonstrate that pp72 is composed of several phosphoproteins and identify p72syk as one component of pp72. These data, together with recent observations in T cells, indicate that the interaction between p72syk-related tyrosine kinases and zeta-related proteins could play an important role in signal transduction.

Amino Acid Sequence↗
PubMed1984

Three cholinergic neuroblastoma hybrid cell lines that form few synapses on myotubes are deficient in acetylcholine receptor aggregation molecules and large dense core vesicles.

Three neuroblastoma X glioma hybrid cell lines that synthesize and release acetylcholine but that form few or no synapses with cultured skeletal muscle cells lack two characteristics of neuroblastoma or hybrid cell lines that do form many synapses with myotubes: large dense core vesicles and the ability to increase the number of nicotinic acetylcholine receptor clusters on co-cultured myotube membranes. Functional synapse formation on myotubes was increased by co-culturing myotubes and cells from one of the defective lines with neuroblastoma cells that induce myotube acetylcholine receptor aggregation but which synthesize little or no acetylcholine.

Animals↗
PubMed1989

A point mutation in the neu oncogene mimics ligand induction of receptor aggregation.

The rat neu gene, which encodes a protein closely related to the epidermal growth factor receptor, is a proto-oncogene that can be converted into an oncogene by a point mutation. Both genes encode proteins with a relative molecular mass of 185,000 but the question of why the neu gene product, p185neu, is oncogenic, whereas the product of c-neu, p185c-neu, is not, remains unanswered. The proteins have several features common to the family of tyrosine kinase growth-factor receptors, including cysteine-rich external domains, a hydrophobic transmembrane region and a cytoplasmic tyrosine kinase domain. The oncogenic p185neu differs from p185c-neu by an amino-acid substitution in the transmembrane region of the glycoprotein: this replacement of valine by glutamic acid at position 664 induces increased intrinsic tyrosine kinase activity which is associated with transformation. Many glycoproteins with charged amino acids in the transmembrane region exist as multimeric complexes at the plasma membrane. We have therefore investigated the association state of both products of the neu gene and show that the oncoprotein p185neu is organized at the plasma membrane primarily in an aggregated form, but that p185c-neu is not. Induction of an aggregated state may mimic aspects of ligand-induced receptor aggregation resulting in enzymatic activation that leads to cellular transformation.

Animals↗
PubMed1985

Membrane-related specializations associated with acetylcholine receptor aggregates induced by electric fields.

The localization of membrane-associated specializations (basal lamina and cytoplasmic density) at sites of acetylcholine receptor (AChR) aggregation is consistent with an involvement of these structures in receptor stabilization. We investigated the occurrence of these specializations in association with AChR aggregates that develop at the cathode-facing edge of Xenopus muscle cells during exposure to a DC electric field. The cultures were labeled with a fluorescent conjugate of alpha-bungarotoxin and the receptor distribution on selected cells was determined before and after exposure to the field. In thin sections taken from the same cells, the cathode-facing edge was characterized by plaques of basal lamina and cytoplasmic density co-extensive with sarcolemma of increased density. In sections cut in a plane similar to the fluorescence image, it was possible to demonstrate that the specializations were concentrated at areas of field-induced AChR aggregation, and at receptor clusters existing on control cells. This finding further indicates that these structures participate in AChR stabilization, and that the mechanisms involved in AChR aggregation that result from field exposure and nerve contact may be similar.

Animals↗
PubMed1995

Randomized, Placebo-Controlled Study of Lamifiban with Thrombolytic Therapy for the Treatment of Acute Myocardial Infarction: Rationale and Design for the Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) Study.

The benefits of thrombolytic therapy in the treatment of acute myocardial infarction are incontrovertible. Large-scale studies combining angiographic and clinical end-points have demonstrated a perfusion-mortality relationship, with the highest survival rate among patients with early restoration of TIMI grade 3 coronary arterial flow. Despite advances in thrombolytic strategies, a substantial number of patients fail to rapidly achieve and maintain adequate coronary perfusion with thrombolysis. Conjunctive therapy with aspirin has proven useful in thrombolytic regimens, likely countering the heightened platelet activity central to acute coronary syndromes. The antiplatelet effect of aspirin is relatively weak compared with that of glycoprotein IIb/IIIa platelet receptor antagonists, which block the final common pathway of platelet aggregation. Lamifiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist. In early experimental studies, Lamifiban in combination with thrombolytic therapy has been shown to effectively restore coronary arterial patency, and phase I and phase II data have shown its use to be safe. To determine the optimal dose with regard to safety and efficacy of Lamifiban to be used with thrombolytic therapy in a large-scale trial, a phase II study is underway. The Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) study is a randomized, placebo-controlled study of Lamifiban in 400 patients receiving thrombolysis as treatment for acute myocardial infarction. By studying 90-minute angiography, platelet aggregation, continuous electrocardiography, and clinical outcome in PARADIGM, important insights will be obtained to determine the optimal dose of Lamifiban for phase III study. We provide the background and rationale for the study of Lamifiban in PARADIGM and other ongoing studies in acute coronary syndromes.

Journal Article↗
PubMed1975

C3-mediated cytoadherence. Formation of C3 receptor aggregates as prerequisite for cell attachment.

Inhibition of free movement of C3 receptors by either applying low temperature (3 degrees C) or fixing the cell surfce of lymphocytes with glutaraldehyde (2 times 10(-5) to 2 times 10(-1)%) results in loss of firm attachment of EAC142 3b cells to the lympocytes as demonstrated here by loss of rosette formation of Raji lymphoid cells. Under the same conditions soluble C3 can still bind but is unable to induce aggregation of C3 receptors into small patches. It is suggested that the local increase of C3 receptor density by aggregation is a prerequisite for C3-dependent cytoadherence. Microaggregation of corresponding receptor sites may be essential also in other recognition systems.

Animals↗
PubMed1998

Laminin and alpha-dystroglycan mediate acetylcholine receptor aggregation via a MuSK-independent pathway.

Specific isoforms of laminin (LN) are concentrated at neuromuscular junctions (NMJs) where they may participate in synaptic organization or function. In myotubes from C2 cells, LN is concentrated within the majority of spontaneous acetylcholine receptor (AChR) aggregates. Neural agrin substantially increases this colocalization, suggesting that agrin can recruit LN into AChR aggregates. Addition of LN to C2 myotubes induces a more than twofold increase in the number of AChR aggregates. These aggregates have a larger size and are more dense than are those induced by agrin, suggesting that LN is involved in the growth and/or stabilization of AChR aggregates. Consistent with this hypothesis, an antiserum to LN reduces the size of individual AChR aggregates but increases their number. In C2 myotubes, extracellular matrix receptors containing the integrin beta1 subunit are poorly colocalized with AChR aggregates, suggesting that integrins may not be involved in LN-induced aggregation. In contrast, almost all AChR aggregates are associated with dystroglycan immunoreactivity, and monoclonal antibody (mAb) IIH6 against alpha-dystroglycan (alpha-DG), a LN and agrin receptor, causes a concentration-dependent inhibition of LN-induced aggregation. Moreover, S27 cells, which lack a functional alpha-DG, and two C2-derived cell lines expressing antisense DG mRNA fail to aggregate AChRs in response to LN. Finally, LN-induced AChR aggregation does not involve the phosphorylation of the muscle-specific tyrosine kinase receptor (MuSK) or the AChR beta subunit. We hypothesize that the interaction of LN with alpha-DG contributes to the growth and/or stabilization of AChR microaggregates into macroaggregates at the developing NMJ via a MuSK-independent mechanism.

Agrin↗
PubMed1998

Combining thrombolysis with the platelet glycoprotein IIb/IIIa inhibitor lamifiban: results of the Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) trial.

OBJECTIVES: The trial was designed to assess the safety, pharmacodynamics and effects on reperfusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor lamifiban when given with thrombolysis to patients with ST segment elevation acute myocardial infarction. BACKGROUND: Studies of fibrinolytic agents in acute myocardial infarction have demonstrated a direct relationship between early complete reperfusion and survival. Blockade of the platelet GP IIb/IIIa receptor complex inhibits platelet aggregation and may speed reperfusion when given in conjunction with thrombolysis to patients with acute myocardial infarction. METHODS: Patients with ST segment elevation presenting within 12 h of symptom onset who were treated with either tissue-plasminogen activator or streptokinase were enrolled in this three-part Phase II dose exploration study. In Part A, all patients received the GP IIb/IIIa inhibitor lamifiban in an open-label, dose escalation scheme. Parts B and C were a randomized, double-blind comparison of a bolus plus 24-h infusion of lamifiban versus placebo with patients randomized in a 2:1 ratio. The goal was to identify a dose(s) of lamifiban that provided >85% adenosine diphosphate (ADP)-induced platelet aggregation inhibition. A composite of angiographic, continuous electrocardiographic and clinical markers of reperfusion was the primary efficacy end point, and bleeding was the primary safety end point. RESULTS: Platelet aggregation was inhibited by lamifiban in a dose-dependent manner with the highest doses exceeding 85% ADP-induced platelet aggregation inhibition. There was more bleeding associated with lamifiban (transfusions in 16.1% lamifiban-treated vs. 10.3% placebo-treated patients). Lamifiban induced more rapid reperfusion as measured by all continuous electrocardiographic (ECG) parameters. CONCLUSIONS: Lamifiban given with thrombolytic therapy appears to be associated with more rapid and complete reperfusion than placebo. As expected in this small sample, there were no obvious clinical benefits to lamifiban over placebo. Reconciliation of ECG monitoring with clinical outcomes will require a larger, adequately powered clinical trial.

Acetates↗
PubMed1993

Insights into the function of a sperm-surface progesterone receptor: evidence of ligand-induced receptor aggregation and the implication of proteolysis.

Human spermatozoa have recently been introduced as a model for the study of rapid, nongenomic effects of steroids on the cell. Indirect evidence suggests the presence of a novel type of progesterone receptor on the cell surface; some cellular responses mediated by the receptor have been shown to be sensitive to protease inhibitors, but the molecular identity and the mode of function of this receptor are not known. Recent biochemical evidence showed that Ca2+ influx and a Ca(2+)-dependent exocytotic event (the acrosome reaction) can be induced in human sperm by antibody-mediated aggregation of the cell-surface progesterone receptor. These data suggested that progesterone receptor aggregation, occurring after ligand binding, may represent an early reaction in the signal transduction pathway. In this study we used cytological methods to examine ligand-induced changes in the distribution of the progesterone receptor in the sperm plasma membrane. We also examined the effects of trypsin and of trypsin inhibitors on the function of the receptor. Under the conditions of this study, neither trypsin nor trypsin inhibitors affected sperm viability, motility, or the acrosome reaction. However, the trypsin treatment completely abolished the ligand-binding activity of the sperm progesterone receptor. On the other hand, trypsin inhibitors did not influence the ligand binding despite their inhibitory effect on the ligand-induced exocytosis. The treatment with trypsin inhibitors was thus used to prevent the exocytotic reaction and so to preserve the plasma membrane for the study of ligand-induced receptor migration. The distribution of ligand-receptor complexes in the sperm acrosomal region remained homogeneous during incubation at 4 degrees C, but warming to 37 degrees C entailed a rapid formation of patches, followed by migration of the complexes towards the sperm equatorial region and ending by a virtually complete disappearance of the complexes from the anterior acrosomal region. It is concluded that aggregation is an early response of the sperm-surface progesterone receptor to ligand binding, that trypsin inhibitors block the function of the receptor downstream of the aggregation, and that some mechanism must exist in the plasma membrane to protect the ligand-binding site from digestion while permitting the protease action in the signal transduction mechanism.

Acrosome↗
PubMed1988

Regulation of agrin-induced acetylcholine receptor aggregation by Ca++ and phorbol ester.

Agrin, a protein extracted from the electric organ of Torpedo californica, induces the formation of specializations on cultured chick myotubes that resemble the postsynaptic apparatus at the neuromuscular junction. The aim of the studies reported here was to characterize the effects of agrin on the distribution of acetylcholine receptors (AChRs) and cholinesterase as a step toward determining agrin's mechanism of action. When agrin was added to the medium bathing chick myotubes small (less than 4 micron 2) aggregates of AChRs began to appear within 2 h and increased rapidly in number until 4 h. Over the next 12-20 h the number of aggregates per myotube decreased as the mean size of each aggregate increased to approximately 15 micron 2. The accumulation of AChRs into agrin-induced aggregates occurred primarily by lateral migration of AChRs already in the myotube plasma membrane at the time agrin was added to the cultures. Aggregates of AChRs and cholinesterase remained as long as agrin was present in the medium; if agrin was removed the number of aggregates declined slowly. The formation and maintenance of agrin-induced AChR aggregates required Ca++, Co++ and Mn++ inhibited agrin-induced AChR aggregation and increased the rate of aggregate dispersal. Mg++ and Sr++ could not substitute for Ca++. Agrin-induced receptor aggregation also was inhibited by phorbol 12-myristate 13-acetate, an activator of protein kinase C, and by inhibitors of energy metabolism. The similarities between agrin's effects on cultured myotubes and events that occur during formation of neuromuscular junctions support the hypothesis that axon terminals release molecules similar to agrin that induce the differentiation of the postsynaptic apparatus.

Agrin↗
PubMed1992

T cell receptor aggregation, but not dimerization, induces increased cytosolic calcium concentrations and reveals a lack of stable association between CD4 and the T cell receptor.

Exposure of T94, a CD4+ V beta 8-expressing murine Th cell clone, or immediately ex vivo CD4+ T cells to deaggregated, bivalent antibodies specific for either the TCR or CD3 failed to induce an increase in [Ca2+]i, or activation of phosphatidylinositol hydrolysis unless cross-linked with a secondary anti-Ig antibody. In contrast, we show that a combination of two mAb directed against different components of the TCR/CD3 complex (145.2C11, anti-CD3 epsilon and F23.1, anti-V beta 8) successfully induce second messenger formation, that is, without any requirement for a secondary antibody. This requirement for either a secondary antibody or two independent bivalent antibodies to activate second messenger production in T cells suggested that the signal transduction apparatus may be activated by multiple TCR/CD3 complexes being brought together on the T cell surface. This was supported by the observation that conditions inducing increased T cell [Ca2+]i through the TCR/CD3 complex also resulted in aggregation of the TCR/CD3 complex on the T cell surface. Conversely, binding of anti-TCR/CD3 antibodies to the T cell under conditions that did not induce increased [Ca2+]i also failed to induce surface TCR/CD3 redistribution. Cross-linking of the CD4 accessory molecule on T94 also resulted in increased [Ca2+]i, with kinetics similar to those observed after TCR/CD3 oligomerization. CD4 is involved in the recognition of invariant regions of MHC class II during Ag presentation and has been proposed to be associated with TCR/CD3 in the absence of Ag. Aggregation of TCR/CD3 and subsequent second messenger formation was achieved by combinations of mAb to distinct determinants within the complex due to the stable association of these determinants within the T cell membrane. We therefore assessed the functional association of CD4 with the TCR/CD3 complex by examining whether a combination of mAb directed against CD4 and CD3 or TCR induced second messenger formation. We found that anti-CD4 in combination with F23.1 or with 145.2C11 failed to induce increases in [Ca2+]i. Furthermore, mAb to CD4 failed to inhibit the increase in [Ca2+]i observed with the combination of 145.2C11 and F23.1. We therefore conclude that CD4 is not stably associated with TCR or CD3 in the absence of Ag/MHC class II composites.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2000

Fas ligand-induced c-Jun kinase activation in lymphoid cells requires extensive receptor aggregation but is independent of DAXX, and Fas-mediated cell death does not involve DAXX, RIP, or RAIDD.

Jun kinase signaling can be elicited by death receptor activation, but the mechanism and significance of this event are still unclear. It has been reported that cross-linking Abs to Fas trigger c-Jun N-terminal kinase (JNK) signaling via caspase-mediated activation of MEKK1 (JNK kinase kinase), elevation of ceramide levels or by recruitment of death domain associated protein (DAXX) to Fas. The effect of physiological ligand for Fas on JNK signaling was never investigated, although evidence is accumulating that Fas ligand is able to induce cellular responses distinct from those evoked by Ab-mediated cross-linking of Fas. Therefore, we investigated the effect of Fas ligand on JNK signaling. Like its ability to induce cell death, Fas ligand reliably activated JNK only upon extensive aggregation of the receptor. Although this was partially dependent on caspase activation, DAXX was not required. DAXX and other death receptor-associated proteins, which have been reported to bind directly or indirectly to Fas, such as receptor interacting protein (RIP) and RIP-associated ICH-1/CED-3-homologous protein with a death domain (RAIDD), were shown to be dispensable for Fas ligand-induced apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed1990

Rapid induction of acetylcholine receptor aggregates by a neural factor and extracellular Ca2+.

A soluble fetal brain extract (EBX) induces acetylcholine receptor (AChR) aggregation in cultured rat myotubes within 4 hr at 36 degrees C in a defined medium containing 1.8 mM (normal) extracellular Ca2+ (Olek et al., 1983). The activity of EBX was Ca2+ dependent; reducing extracellular Ca2+ significantly inhibited EBX-induced AChR aggregation and a 15-50% increase in extracellular Ca2+ synergistically enhanced the activity of EBX. Synergism was specific for Ca2+ as increases in other divalent cations (Ba2+, Co2+, Mg2+, Mn2+, Sr2+) had no effect. A large increase (300-500%) in extracellular Ca2+ alone also induced AChR aggregation within 4 hr at 36 degrees C. An equivalent increase in other cations (Ba2+, Co2+, Mg2+, Mn2+, Sr2+) did not promote AChR aggregation. An initial 15-min pulse of increased extracellular Ca2+ alone or with EBX was adequate to induce AChR aggregation. Aggregates induced by EBX, Ca2+ alone, or EBX/Ca2+ were found predominantly on the top surface of the myotube. These treatments did not detectably alter preexisting aggregates present at substrate contact sites on the bottom surface of myotubes. AChR aggregation induced by any treatment was not inhibited by cycloheximide, Ca2+ channel blockers, or protease inhibitors but was blocked by Co2+ and sodium azide.

Animals↗