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Related Concept Videos

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...
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Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
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Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
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General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...

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Tgf-Beta signaling in development.

Krit Kitisin1, Tapas Saha, Tiffany Blake

  • 1Laboratory of Cancer Genetics and Digestive Diseases, Department of Surgery, and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.

Science'S STKE : Signal Transduction Knowledge Environment
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Summary

The transforming growth factor-beta (TGF-beta) superfamily and bone morphogenetic proteins (BMPs) are crucial for stem cell fate and tumor suppression. Their combined signaling precisely defines stem cell commitment and influences cancer progression.

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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Area of Science:

  • Cellular and Molecular Biology
  • Developmental Biology
  • Cancer Research

Background:

  • The transforming growth factor-beta (TGF-beta) superfamily includes nearly 30 growth and differentiation factors, such as TGF-betas, activins, inhibins, and bone morphogenetic proteins (BMPs).
  • Multiple TGF-beta superfamily members play critical roles in regulating embryonic stem (ES) cell biology, including fate commitment, self-renewal, and differentiation.
  • These factors also exhibit significant roles in tumor suppression and can influence cancer progression.

Purpose of the Study:

  • To integrate and describe the signaling pathways activated by TGF-beta, BMPs, nodal, and activin in mammalian development.
  • To elucidate the precise mechanisms by which these signaling pathways define stem cell fate commitment.
  • To highlight the role of these signaling pathways in cancer suppression and progression as potential therapeutic targets.

Main Methods:

  • Integration of signaling pathways from TGF-beta, BMP, nodal, and activin using the Database of Cell Signaling's Connections Map Pathway.
  • Analysis of evidence primarily from studies on mouse and human embryonic stem cells.
  • Inclusion of data from mouse knockout studies to understand in vivo functions.

Main Results:

  • TGF-beta superfamily members exhibit diverse roles, inhibiting hematopoietic progenitor proliferation, promoting neural precursor lineage commitment, and suppressing epithelial tumors.
  • BMPs block neural differentiation in mouse and human ES cells, support mouse ES cell self-renewal, and contribute to tumor suppression.
  • The intricate cross-talk among intracellular signaling pathways activated by these ligands precisely defines stem cell fate commitment.

Conclusions:

  • The combined signaling of TGF-beta superfamily members, including BMPs, nodal, and activin, is fundamental to mammalian development and stem cell biology.
  • Understanding these complex signaling networks is crucial for deciphering stem cell fate and identifying molecular effectors involved in cancer.
  • These signaling pathways represent potential therapeutic targets for cancer intervention, either for suppression or to modulate progression.