Major Ligand (major + ligand)

Distribution by Scientific Domains

Selected Abstracts

SLIC-1/sorting nexin,20: A novel sorting nexin that directs subcellular distribution of PSGL-1

Abstract P-Selectin glycoprotein ligand-1 (PSGL-1) is a mucin-like glycoprotein expressed on the surface of leukocytes that serves as the major ligand for the selectin family of adhesion molecules and functions in leukocyte tethering and rolling on activated endothelium and platelets. Previous studies have implicated the highly conserved cytoplasmic domain of PSGL-1 in regulating outside-in signaling of integrin activation. However, molecules that physically and functionally interact with this domain are not completely defined. Using a yeast two-hybrid screen with the cytoplasmic domain of PSGL-1 as bait, a novel protein designated selectin ligand interactor cytoplasmic-1 (SLIC-1) was isolated. Computer-based homology search revealed that SLIC-1 was the human orthologue for the previously identified mouse sorting nexin,20. Direct interaction between SLIC-1 and PSGL-1 was specific as indicated by co-immunoprecipitation and motif mapping. Colocalization experiments demonstrated that SLIC-1 contains a Phox homology domain that binds phosphoinositides and targets the PSGL-1/SLIC-1 complex to endosomes. Deficiency in the murine homologue of SLIC-1 did not modulate PSGL-1-dependent signaling nor alter neutrophil adhesion through PSGL-1. We conclude that SLIC-1 serves as a sorting molecule that cycles PSGL-1 into endosomes with no impact on leukocyte recruitment. [source]

Regulation of epithelial cell cytokine responses by the ,3,1 integrin

IMMUNOLOGY, Issue 2 2003
Farah D. Lubin
Summary Epithelial cells (EC) from various tissues can produce important cytokines and chemokines when stimulated by proinflammatory cytokines. These EC also receive signals from cell surface integrins, like the ,3,1 integrin, which is important in cell migration and wound healing of epithelial monolayers. However, little is known of the effect of integrin signals on cytokine responses by EC. Colonic Caco-2 cells treated with an anti-,3 integrin antibody prior to stimulation with the proinflammatory cytokine interleukin (IL)-1 yielded suppressed levels of mRNA and secreted IL-6, IL-8 and monocyte chemoattractant protein-1 as compared to cells treated with normal mouse immunoglobulin G. Lung A549 cells also showed a similar suppression of cytokine secretion. Likewise, treatment of the Caco-2 cells with the same antibody suppressed tumour necrosis factor-,-stimulated IL-6 secretion. Fab fragments of the anti-,3 integrin antibody did not induce the suppressive effect but did block the suppressive effect of the whole antibody suggesting that the effect of the antibody required cross-linking of the integrins. Finally, culture of the Caco-2 cells on laminin type 5 (the major ligand for this integrin) yielded depressed levels of IL-1-induced IL-6 secretion as compared to cells on laminin type 1. These data are the first indication that the ,3,1 integrin may cause a suppression of cytokine responses by EC which may be important in regulating the capacity of EC to respond during inflammation or wound healing. [source]

ORIGINAL ARTICLE: Effect of Progesterone on HLA-E Gene Expression in JEG-3 Choriocarcinoma Cell Line

Zhongying Huang
Problem, Among class Ib human leukocyte antigen (HLA) molecules, HLA-E is known to be a major ligand of CD94/NKG2 receptor on natural killer (NK) cells, and to play a pivotal role in recognition of extravillous trophoblasts (EVTs) by maternal immune cells. However, it is scarcely known how HLA-E expression is regulated in EVTs. Method of study, In this study, we investigated whether progesterone, an essential hormone in maintaining pregnancy, regulated HLA-E expression in EVT-like cell line, JEG-3. HLA-E mRNA amount in cultured JEG-3 cells was assessed by real-time PCR and cell-surface HLA-E protein was analyzed by flowcytometry. Results, Real-time PCR showed 3.5-fold increase 1 hour after the addition of 1000 ng/ml progesterone. This response was dimished by the addition of RU486, an antagonist for progesterone receptor. Flowcytometry indicated that 1000 ng/ml progesterone slightly enhanced HLA-E expression on the surface of JEG-3. Conclusion, These results suggest that progesterone up-regulates HLA-E expression in JEG-3 cells through the pathway mediated by progesterone receptor. Our findings might give a new insight into immunomodulatory function of progesterone at fetomaternal interface. [source]

Structure of the heterodimeric neurotoxic complex viperotoxin F (RV-4/RV-7) from the venom of Vipera russelli formosensis at 1.9, resolution

Markus Perbandt
The presynaptic viperotoxin F is the major lethal component of the venom of Vipera russelli formosensis (Taiwan viper). It is a heterodimer of two highly homologous (65% identity) but oppositely charged subunits: a basic and neurotoxic PLA2 (RV-4) and an acidic non-toxic component with a very low enzymatic activity (RV-7). The crystal structure of the complex has been determined by molecular replacement and refined to 1.9, resolution and an R factor of 22.3% with four RV-4/RV-7 complexes in the asymmetric unit, which do not exhibit any local point-group symmetry. The complex formation decreases the accessible surface area of the two subunits by ,1425,2. Both PLA2s are predicted to have very low, if any, anticoagulant activity. The structure of viperotoxin F is compared with that of the heterodimeric neurotoxin vipoxin from the venom of another viper, V. ammodytes meridionalis. The structural basis for the differences between the pharmacological activities of the two toxins is discussed. The neutralization of the negative charge of the major ligand for Ca2+, Asp49, by intersubunit salt bridges is probably a common mechanism of self-stabilization of heterodimeric Viperinae snake-venom neurotoxins in the absence of bound calcium. [source]

Different proportions of cadmium occur as Cd-binding phytochelatin complexes in plants

Eduardo Marentes
The aim was to determine cadmium (Cd) speciation in various plants, between buffer-soluble and acid-soluble Cd, and also within the buffer-soluble Cd. A better understanding of Cd speciation shows the relative importance of different biological mechanisms for Cd sequestration. Roots of Pistia stratiodes, Eichhornia crassipes, Agrostis gigantea, Deschampsia caespitosa and wheat Triticum turgidum var. durum were analyzed. Buffer extractions solubilized varying proportions of Cd, ranging from 12% in Eichhornia to 83% in Agrostis. The proportion increased with time of Cd exposure in Pistia. It also increased in wheat roots as the external Cd rose from 0.05 to 0.5 ,M and was lowest in old leaves and highest in roots. The remaining Cd was extractable with acid. Gel filtration resolved buffer-soluble Cd into three peaks distinct from inorganic Cd. Two complexes with phytochelatins and related polythiols were present in all cases, inorganic Cd being prominent only in Eichhornia extracts. The phytochelatin complexes accounted for 2% of the root Cd in Eichhornia to 78% in Agrostis. In wheat, phytochelatins bound 82% of the Cd in roots, 19% in young leaves and 12% in old leaves. The cysteine-rich protein metallothionein from wheat was detected immunologically in the void volume of gel filtrations of old and young leaves, but not of roots, and was distinct from the two phytochelatin-based complexes. Speciation of Cd in the various plants indicated that phytochelatins were not necessarily the major ligands of Cd. [source]