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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Hedgehog Signaling Pathway02:33

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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Interactions Between Signaling Pathways01:19

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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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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Canonical Wnt Signaling Pathway02:54

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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...
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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
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Signaling pathways as linear transmitters.

Harry Nunns1, Lea Goentoro1

  • 1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.

Elife
|September 18, 2018
PubMed
Summary

Three major cell signaling pathways unexpectedly exhibit linear signal transmission, similar to engineered systems. This research reveals how complex biological networks achieve this conserved behavior through distinct mechanisms.

Keywords:
cell biologycomputational biologyhuman cell lineslinearitysignal transmissionsignaling pathwayssystems biology

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Area of Science:

  • Cellular biology
  • Systems biology
  • Biophysics

Background:

  • Biological networks, such as signaling pathways, are complex and challenging to understand.
  • Signaling pathways are crucial for cellular communication and function.
  • Mathematical models are valuable tools for analyzing pathway behavior.

Purpose of the Study:

  • To analyze mathematical models of three key metazoan signaling pathways: Wnt, MAPK/ERK, and Tgfβ.
  • To investigate the input-output behavior of these pathways and identify common properties.
  • To experimentally validate the predicted behaviors and underlying mechanisms.

Main Methods:

  • Mathematical modeling of Wnt, MAPK/ERK, and Tgfβ signaling pathways.
  • Analysis of model outputs to identify linear signal transmission properties.
  • Experimental validation of linear behavior in Wnt and ERK pathways.
  • Investigating the distinct mechanisms driving linearity in each pathway.

Main Results:

  • Unexpected convergence: Wnt, MAPK/ERK, and Tgfβ pathways exhibit linear signal transmission in certain physiological contexts.
  • Experimental confirmation of linear input-output behavior in Wnt and ERK pathways.
  • Distinct molecular mechanisms underlie linearity in each pathway, despite the convergent behavior.

Conclusions:

  • Complex biological signaling networks can converge on simple, predictable behaviors like linearity.
  • Linearity in signaling pathways facilitates faithful signal transmission, analogous to engineered systems.
  • Understanding these conserved behaviors provides insights into cellular information processing and network design.