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Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
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TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...

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Related Experiment Video

Updated: Jun 2, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

How ITAMs inhibit signaling.

Lionel B Ivashkiv1

  • 1Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, 535 East 70th Street, New York, NY 10021, USA. ivashkivl@hss.edu

Science Signaling
|April 21, 2011
PubMed
Summary
This summary is machine-generated.

Low avidity engagement of immunoglobulin A receptor FcαRI (FcαRI) triggers inhibitory signaling. This process involves FcαRI and SHP-1 recruitment to lipid rafts, leading to immune cell deactivation.

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Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
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Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy

Published on: September 29, 2016

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Last Updated: Jun 2, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
12:24

Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy

Published on: September 29, 2016

Area of Science:

  • Immunology
  • Cell Signaling
  • Molecular Biology

Background:

  • Immunoreceptor tyrosine-based activation motifs (ITAMs) mediate immune cell activation.
  • ITAM-associated receptors can exert inhibitory functions, crucial for regulating inflammation.
  • The precise mechanisms underlying ITAM-mediated inhibitory signaling remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which ITAM-associated receptors mediate inhibitory signaling.
  • To investigate the role of FcαRI and SHP-1 in immune cell regulation.

Main Methods:

  • Investigated FcαRI-mediated signaling using low avidity ligation.
  • Utilized techniques to track FcαRI and SHP-1 localization within immune cells.
  • Examined receptor trafficking and colocalization within specific cellular compartments.

Main Results:

  • Low avidity ligation of FcαRI induces its translocation to membrane lipid rafts along with SHP-1.
  • Activating receptors colocalize with FcαRI and SHP-1 upon subsequent ligation.
  • Receptor complexes are trafficked to an inhibitory compartment, the inhibisome, where SHP-1 deactivates signaling molecules.

Conclusions:

  • ITAM suppressive signals hijack the function of lipid rafts to promote receptor aggregation.
  • This aggregation within supramolecular domains leads to deactivation of signaling pathways by SHP-1.
  • FcαRI-mediated signaling provides a novel mechanism for immune cell inhibition.