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Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:

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Related Experiment Video

Updated: Jul 3, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Protein interaction data set highlighted with human Ras-MAPK/PI3K signaling pathways.

Jian Wang1, Yanzhi Yuan, Ying Zhou

  • 1State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.

Journal of Proteome Research
|July 16, 2008
PubMed
Summary

Researchers mapped protein interactions in Ras-MAPK and PI3K-AKT pathways, revealing a network linking these crucial signaling cascades to cellular processes. Five key interactions were validated in mammalian cells, enhancing understanding of pathway mechanisms.

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Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

Related Experiment Videos

Last Updated: Jul 3, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Systems Biology

Background:

  • Ras-MAPK and PI3K-AKT pathways are fundamental signaling cascades in metazoans.
  • These pathways regulate numerous physiological and pathological processes.
  • Understanding their molecular mechanisms is crucial for biological and medical research.

Purpose of the Study:

  • To construct a protein interaction network for human Ras-MAPK/PI3K pathway components.
  • To identify novel protein-protein interactions (PPIs) within these signaling networks.
  • To gain deeper insights into the molecular intricacies of Ras-MAPK/PI3K signaling.

Main Methods:

  • Yeast two-hybrid screening of 42 independent cDNA libraries.
  • Bioinformatic analysis to assess interaction confidence.
  • Co-immunoprecipitation and colocalization assays for in vivo validation.

Main Results:

  • Identified 200 protein-protein interaction (PPI) pairs among 180 molecules.
  • Discovered a large protein cluster with 193 PPIs involving 169 proteins.
  • Found 74 high-confidence interactions and enrichment of Gene Ontology terms related to stress response.

Conclusions:

  • The study presents a comprehensive protein interaction network for Ras-MAPK/PI3K pathways.
  • The network links Ras signaling to diverse cellular processes.
  • Validated interactions provide in vivo evidence, advancing the understanding of pathway regulation.