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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...
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 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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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 the...
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...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...

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Related Experiment Video

Updated: Jul 11, 2026

Identification of Kinase-substrate Pairs Using High Throughput Screening
11:13

Identification of Kinase-substrate Pairs Using High Throughput Screening

Published on: August 29, 2015

Dissecting kinase signaling pathways.

Scott N Boyle1, Anthony J Koleske

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, United States.

Drug Discovery Today
|September 11, 2007
PubMed
Summary

Identifying protein kinase substrates is challenging but crucial for discovering new drug targets for diseases like cancer. This review discusses methods for substrate identification and proposes criteria for validating their physiological relevance.

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Last Updated: Jul 11, 2026

Identification of Kinase-substrate Pairs Using High Throughput Screening
11:13

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Published on: August 29, 2015

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant protein kinase signaling is implicated in numerous human diseases, including cancer, diabetes, and neurological disorders.
  • Kinase inhibitors are effective treatments, suggesting kinase pathways offer potential for novel drug target discovery.
  • Identifying protein kinase substrates is complex due to conserved phosphorylation mechanisms and substrate promiscuity.

Purpose of the Study:

  • To review and compare various techniques for identifying protein kinase substrates.
  • To address the challenges in validating identified substrates as physiologically relevant.
  • To propose criteria for confirming the physiological significance of kinase-substrate interactions.

Main Methods:

  • Review of existing literature on protein kinase substrate identification techniques.
  • Analysis of the advantages and disadvantages of different methodologies.
  • Development of a framework for validating putative kinase substrates.

Main Results:

  • Several techniques exist for identifying kinase substrates, each with unique strengths and weaknesses.
  • Validation of identified substrates as physiologically relevant remains a significant hurdle.
  • Proposed criteria offer a systematic approach to confirm the biological importance of kinase-substrate interactions.

Conclusions:

  • Effective identification and validation of kinase substrates are essential for advancing therapeutic strategies.
  • Understanding kinase signaling pathways can uncover non-kinase drug targets.
  • The proposed validation criteria aim to enhance the reliability of substrate identification in disease research.