scholarly journals Membrane distributions of two ligand-binding receptor complexes in the CLAVATA pathway

2010 ◽  
Vol 5 (11) ◽  
pp. 1442-1445 ◽  
Author(s):  
Yongfeng Guo ◽  
Steven E. Clark
Keyword(s):  
Ligand Binding ◽  
Receptor Complexes

scholarly journals Dap10 and Dap12 Form Distinct, but Functionally Cooperative, Receptor Complexes in Natural Killer Cells

2000 ◽  
Vol 192 (7) ◽  
pp. 1059-1068 ◽  
Author(s):  
Jun Wu ◽  
Holly Cherwinski ◽  
Thomas Spies ◽  
Joseph H. Phillips ◽  
Lewis L. Lanier
Keyword(s):  
Ligand Binding ◽  
Nk Cells ◽  
Natural Killer ◽  
Tyrosine Kinases ◽  
Nk Cell ◽  
Adaptor Proteins ◽  
Transmembrane Segments ◽  
Receptor Complexes ◽  
Activating Receptors ◽  
Specific Association

Many of the activating receptors on natural killer (NK) cells are multisubunit complexes composed of ligand-binding receptors that are noncovalently associated with membrane-bound signaling adaptor proteins, including CD3ζ, FcεRIγ, DAP12, and DAP10. Because the DAP10 and DAP12 genes are closely linked, expressed in NK cells, and have remarkably similar transmembrane segments, it was of interest to determine the specificity of their interactions with ligand-binding receptors and to examine their signaling properties. Despite their similarities, DAP10, DAP12, FcεRIγ, and CD3ζ form specific receptor complexes with their ligand-binding partners in NK cells and transfectants. The transmembrane regions of DAP10 and DAP12 are sufficient to confer specific association with their partners. Although cross-linking of either DAP10- or DAP12-associated receptors has been shown to be sufficient to trigger NK cell–mediated cytotoxicity against Fc receptor–bearing cells, substantial synergy was observed in the induction of cytokine production when both receptors were engaged. Activation of the Syk/ZAP70 tyrosine kinases by the immunoreceptor tyrosine-based activation motif–containing DAP12 adaptor and of the phosphatidylinositol 3-kinase pathway by the YxNM-containing DAP10 adaptor may play an important role in the stimulation of NK cells and T cells.

Regulation of interacting populations during endocytosis: models of growth factor-tumor promoter dynamics

1986 ◽  
Vol 250 (6) ◽  
pp. R1123-R1132
Author(s):  
M. Gex-Fabry ◽  
C. DeLisi
Keyword(s):  
Growth Factor ◽  
Ligand Binding ◽  
Phorbol Ester ◽  
Egf Receptor ◽  
Phorbol Esters ◽  
Time Lag ◽  
Tumor Promoter ◽  
Necessary Condition ◽  
Coated Pits ◽  
Receptor Complexes

A model of growth factor-cell receptor interactions, including internalization, sorting, recycling, and degradation and their modulation by tumor promoters, is developed, analyzed, and tested. In keeping with data and concepts based on a large number of systems, the main assumption is that after receptor-ligand binding the complex associates with a second membrane protein, localized in coated pits, and that this event is a necessary condition for receptor-mediated endocytosis and subsequent intracellular processes. As a consequence of the model, ligands having distinct receptors interfere at the cell surface through competition between their receptor complexes for a limited pool of coated pit proteins. The utility of the model is illustrated by a detailed analysis of binding, endocytosis, and degradation of epidermal growth factor (EGF) and their modulation by phorbol esters. The analysis permits quantitative characterization of the dynamics of the endocytic processes and leads to the following conclusions. The Scatchard plot changes from linear to nonlinear as the ratio of the number of coated pit proteins to the number of receptors decreases. Competition between phorbol ester and EGF-bound receptors for coated pit proteins predicts, in agreement with observation, conversion of nonlinear EGF Scatchard plots to linear plots subsequent to reincubation with phorbol esters. The postulated competition suggests a local homology between the phorbol ester receptor and the EGF receptor. Homologous and heterologous downregulations observed in numerous systems are natural consequences of the model. Preincubation with the heterologous ligand increases the time lag between ligand binding and lysosomal degradation and alters intracellular sorting.

scholarly journals Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. 355-362 ◽  
Author(s):  
Yan Zhao ◽  
Shanshuang Chen ◽  
Adam C. Swensen ◽  
Wei-Jun Qian ◽  
Eric Gouaux
Keyword(s):  
Molecular Structure ◽  
Electron Microscopy ◽  
Signal Transduction ◽  
Ligand Binding ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Mammalian Brain ◽  
Receptor Complexes ◽  
Cryo Electron Microscopy ◽  
Chemical Synapses

Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric assemblies composed of four subunits, GluA1–GluA4. Despite decades of study, the subunit composition, subunit arrangement, and molecular structure of native AMPA receptors remain unknown. Here we elucidate the structures of 10 distinct native AMPA receptor complexes by single-particle cryo–electron microscopy (cryo-EM). We find that receptor subunits are arranged nonstochastically, with the GluA2 subunit preferentially occupying the B and D positions of the tetramer and with triheteromeric assemblies comprising a major population of native AMPA receptors. Cryo-EM maps define the structure for S2-M4 linkers between the ligand-binding and transmembrane domains, suggesting how neurotransmitter binding is coupled to ion channel gating.

scholarly journals Functional differences between two Fc receptor ITAM signaling motifs

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3302-3307 ◽  
Author(s):  
IE Van den Herik-Oudijk ◽  
MW Ter Bekke ◽  
MJ Tempelman ◽  
PJ Capel ◽  
JG Van de Winkel
Keyword(s):  
Ligand Binding ◽  
Antigen Presentation ◽  
Interleukin 2 ◽  
Fc Receptor ◽  
Gamma Chain ◽  
Alpha Chain ◽  
Receptor Complexes ◽  
Functional Differences ◽  
Cytoplasmic Tails ◽  
Chimeric Molecules

Most Ig receptors exist as multi-subunit complexes with a unique ligand binding alpha chain and a common signaling FcR gamma-chain. The myeloid Fc gamma RIIa (CD32) appears unique among FcR because both ligand- binding and signaling capacity are found in the alpha chain. Within the cytoplasmic tails of Fc gamma RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyrosines play an important role. Previously, Fc gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory functions in IIA1.6 B-cell transfectants. Triggering of interleukin-2 (IL-2) release and antigen presentation was absent in Fc gamma RIIa, but not in FcR gamma-chain receptor complexes. We now assessed the capacity of Fc gamma RIIa wild-type and Fc gamma RIIa/gamma chimeric molecules to trigger IL-2 production and antigen presentation by B cells. Both of these functions could solely be triggered by receptors containing the FcRIIa was capable of functional interaction with FcR gamma-chain, thus reconstituting the capacity to trigger IL-2 release and antigen presentation. These data document qualitative differences between Fc receptor ITAMs.

A monoclonal antibody to mammalian angiotensin II AT1 receptor recognizes one of the angiotensin II receptor isoforms expressed by the eel (Anguilla anguilla)

1996 ◽  
Vol 16 (1) ◽  
pp. 45-56 ◽  
Author(s):  
S Marsigliante ◽  
A Muscella ◽  
S Vilella ◽  
G Nicolardi ◽  
L Ingrosso ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Angiotensin Ii ◽  
Ligand Binding ◽  
Molecular Mass ◽  
Chloride Cells ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Receptor Complexes ◽  
Intestinal Membrane ◽  
Liver Membranes

ABSTRACT Using labelled ligand-binding methods, previous studies have identified specific angiotensin II receptors (Ang II-Rs) in eel liver, kidney and intestine membranes. Isoelectric focusing on polyacrylamide gels also showed that there are two Ang II-R isoforms in eel liver, focusing at isoelectric points (pI) 6·5 and 6·7. These may have different functions. In contrast, eel enterocyte plasma membrane and renal brush border membranes contain only the pI 6·5 form. To characterize the eel receptors more fully, a newly developed monoclonal antibody (6313/G2) which selectively recognizes the AT1 subtype of mammalian Ang II-R was used. In ligand-binding experiments, the preincubation of eel liver membranes with 6313/G2 antibody eliminated the specific [3,5-3H]Tyr4-Ile5-Ang II binding. Moreover, Ang II—receptor complexes from solubilized liver membranes, which were immunoprecipitated by 6313/G2-coated beads, had a pI of 6·5. In immunoblotting experiments, the antibody recognized the isoform focusing at pI 6·5 in eel intestine and liver preparations, but not the liver pI 6·7 isoform. Immunoblotting of SDS gels showed that the antibody bound to a single protein of molecular mass of 75 kDa in eel liver, gill and kidney and to a doublet of molecular mass of about 74 and 75 kDa in intestinal membrane preparations. Immunocytochemistry of paraffin-embedded and cryostat sections of eel liver, kidney, intestine and gill showed that antibody 6313/G2 bound to uniformly distributed intracellular sites and cell surface membranes in proximal tubular cells, absorptive intestinal cells, hepatocytes and chloride cells. It also stained endothelium and both the longitudinal and circular layers of smooth muscle cells in the intestine. The data suggest that the previously described Ang II-R from eel liver, kidney and intestine may be similar to the mammalian AT1 subtype.

Kinetic evidence for tandemly arranged ligand binding sites in melanocortin 4 receptor complexes

2006 ◽  
Vol 49 (5) ◽  
pp. 533-542 ◽  
Author(s):  
Sergei Kopanchuk ◽  
Santa Veiksina ◽  
Felikss Mutulis ◽  
Ilze Mutule ◽  
Sviatlana Yahorava ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Sites ◽  
Receptor Complexes ◽  
Melanocortin 4 Receptor ◽  
Ligand Binding Sites

CLiBE: a database of computed ligand binding energy for ligand–receptor complexes

2002 ◽  
Vol 26 (6) ◽  
pp. 661-666 ◽  
Author(s):  
X. Chen ◽  
Z.L. Ji ◽  
D.G. Zhi ◽  
Y.Z. Chen
Keyword(s):  
Binding Energy ◽  
Ligand Binding ◽  
Receptor Complexes

scholarly journals The Helix 1-3 Loop in the Glucocorticoid Receptor LBD Is a Regulatory Element for FKBP Cochaperones

2013 ◽  
Vol 27 (7) ◽  
pp. 1020-1035 ◽  
Author(s):  
Carmel Cluning ◽  
Bryan K. Ward ◽  
Sarah L. Rea ◽  
Ajanthy Arulpragasam ◽  
Peter J. Fuller ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Receptor Activity ◽  
Hek293 Cells ◽  
Global Changes ◽  
Nuclear Targeting ◽  
Receptor Complexes

Abstract The heat-shock protein 90 (Hsp90) cochaperone FK506-binding protein 52 (FKBP52) upregulates, whereas FKBP51 inhibits, hormone binding and nuclear targeting of the glucocorticoid receptor (GR). Decreased cortisol sensitivity in the guinea pig is attributed to changes within the helix 1 to helix 3 (H1-H3) loop of the guinea pig GR (gpGR) ligand-binding domain. It has been proposed that this loop serves as a contact point for FKBP52 and/or FKBP51 with receptor. We examined the role of the H1-H3 loop in GR activation by FKBP52 using a Saccharomyces cerevisiae model. The activity of rat GR (rGR) containing the gpGR H1-H3 loop substitutions was still potentiated by FKBP52, confirming the loop is not involved in primary FKBP52 interactions. Additional assays also excluded a role for other intervening loops between ligand-binding domain helices in direct interactions with FKBP52 associated with enhanced receptor activity. Complementary studies in FKBP51-deficient mouse embryo fibroblasts and HEK293 cells demonstrated that substitution of the gpGR H1-H3 loop residues into rGR dramatically increased receptor repression by FKBP51 without enhancing receptor-FKBP51 interaction and did not alter recruitment of endogenous Hsp90 and the p23 cochaperone to receptor complexes. FKBP51 suppression of the mutated rGR did not require FKBP51 peptidylprolyl cis-trans isomerase activity and was not disrupted by mutation of the FK1 proline-rich loop thought to mediate reciprocal FKBP influences on receptor activity. We conclude that the gpGR-specific mutations within the H1-H3 loop confer global changes within the GR-Hsp90 complex that favor FKBP51 repression over FKBP52 potentiation, thus identifying the loop as an important target for GR regulation by the FKBP cochaperones.

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