Receptor

About: Receptor is a research topic. Over the lifetime, 159318 publications have been published within this topic receiving 8299881 citations.

Signalling through the high-affinity IgE receptor Fc epsilonRI.

Abstract: The Fc epsilonRI complex forms a high-affinity cell-surface receptor for the Fc region of antigen-specific immunoglobulin E (IgE) molecules. Fc epsilonRI is multimeric and is a member of a family of related antigen/Fc receptors which have conserved structural features and similar roles in initiating intracellular signalling cascades. In humans, Fc epsilonRI controls the activation of mast cells and basophils, and participates in IgE-mediated antigen presentation. Multivalent antigens bind and crosslink IgE molecules held at the cell surface by Fc epsilonRI. Receptor aggregation induces multiple signalling pathways that control diverse effector responses. These include the secretion of allergic mediators and induction of cytokine gene transcription, resulting in secretion of molecules such as interleukin-4, interleukin-6, tumour-necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor. Fc epsilonRI is therefore central to the induction and maintenance of an allergic response and may confer physiological protection in parasitic infections.

Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.

Abstract: The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli.