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Related Concept Videos

MAPK Signaling Cascades01:07

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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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...
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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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MAP kinase modules: the excursion model and the steps that count.

Alexander T Piala1, John M Humphreys1, Elizabeth J Goldsmith1

  • 1Department of Biophysics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.

Biophysical Journal
|November 25, 2014
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Summary
This summary is machine-generated.

Mitogen-activated protein (MAP) kinase pathways use sequential dual phosphorylation for signal processing. This ordered mechanism explains steep signal-to-response curves and delayed cellular responses.

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Area of Science:

  • Cellular signaling and signal transduction pathways.
  • Biochemistry and enzymology of kinase cascades.
  • Systems biology and mathematical modeling of biological processes.

Background:

  • MAP kinase modules transmit extracellular signals to cellular effectors.
  • Dual phosphorylation reactions are critical for pathway switch behavior.
  • Understanding the precise mechanism of these reactions is key to deciphering cellular responses.

Purpose of the Study:

  • To review recent signal-to-response studies in cells and in vitro.
  • To reconcile experimental data with physical and mathematical models.
  • To elucidate the sequential nature of dual phosphorylation in MAP kinase cascades.

Main Methods:

  • Review of recent signal-to-response studies.
  • Reconciliation of data with physical models.
  • Analysis of mathematical and theoretical predictions.
  • Biochemical analysis of phosphorylation events.

Main Results:

  • MAP kinase dual phosphorylation reactions are sequential at both cascade levels.
  • Phosphorylation order suggests a shift from Ser/Thr kinase to Tyr kinase activity.
  • Ordered mechanism aligns with predictions for steep signal-to-response curves and delayed responses.

Conclusions:

  • The sequential nature of MAP kinase phosphorylation is crucial for generating specific cellular responses.
  • Understanding the order of events provides insights into pathway regulation.
  • This mechanism supports the generation of steep and delayed signal responses.