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Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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Receptor Downregulation in MVBs01:15

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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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The JAK-STAT Signaling Pathway01:20

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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...
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TGF - β Signaling Pathway01:16

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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...
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Multi-pass Transmembrane Proteins and β-barrels01:09

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In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
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The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities.

Winnie L Kan1, Claire M Weekley2,3, Tracy L Nero2,3

  • 1Cytokine Receptor Laboratory, Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.

Immunological Reviews
|January 3, 2025
PubMed
Summary
This summary is machine-generated.

Cytokine receptor signaling is complex, with distinct biological signals arising from different interleukin-3 (IL-3) receptor assemblies. Understanding these structural nuances paves the way for targeted protein engineering in precision medicine.

Keywords:
crystal structurescytokinegranulocyte‐macrophage colony‐stimulating factorinterleukin‐3interleukin‐5receptor signaling

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Area of Science:

  • Immunology
  • Structural Biology
  • Cell Biology

Background:

  • Cytokines are key regulators of hematopoietic cell growth and activity.
  • The beta common (βc) cytokine receptor family exemplifies heterodimeric receptor systems.
  • Cytokine receptor signaling is not binary; subtle complex alterations yield differential signaling.

Purpose of the Study:

  • To investigate the structural basis of differential signaling in the IL-3 receptor.
  • To explore the formation of higher-order assemblies in cytokine receptor complexes.
  • To link structural insights to potential theranostic applications in precision medicine.

Main Methods:

  • X-ray crystallography and cryo-electron microscopy for structural analysis.
  • Cell biology studies to investigate signaling pathways.
  • Analysis of cytokine:receptor complex formation and oligomerization.

Main Results:

  • The IL-3 receptor ternary complex forms higher-order assemblies, similar to the GM-CSF receptor.
  • Functionally distinct biological signals originate from different IL-3 receptor oligomeric assemblies.
  • Structural insights reveal mechanisms of selective cytokine signaling.

Conclusions:

  • Cytokine receptor signaling complexity is mediated by oligomeric assembly.
  • Structural understanding enables mechanism-based manipulation of cytokine signaling.
  • Targeted protein engineering based on structural data holds promise for precision medicine and theranostics.