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Related Concept Videos

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...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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...
Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...

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Optogenetic Signaling Activation in Zebrafish Embryos
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Mapping preconditioning's signaling pathways: an engineering approach.

James M Downey1, Thomas Krieg, Michael V Cohen

  • 1Department of Physiology and Medicine, University of South Alabama, Mobile, AL 36688, USA. jdowney@usouthal.edu

Annals of the New York Academy of Sciences
|April 1, 2008
PubMed
Summary
This summary is machine-generated.

Heart preconditioning protects against infarction via complex signaling pathways. Mapping these pathways reveals drug targets to trigger this protective state, offering clinical potential.

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Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Signal Transduction

Background:

  • Brief ischemia-reperfusion preconditioning confers resistance to myocardial infarction.
  • The precise arrangement of signal transduction components mediating this protection is largely unknown.
  • Understanding these pathways is crucial for clinical translation of cardioprotection.

Purpose of the Study:

  • To map the signal transduction pathways responsible for ischemia-reperfusion preconditioning-induced cardioprotection.
  • To elucidate the order and interactions of signaling components.
  • To identify potential drug targets for triggering the protected phenotype.

Main Methods:

  • System analysis by injecting signals at intermediate points and monitoring downstream effects.
  • Investigating trigger and mediator phases of the preconditioning response.
  • Utilizing knowledge of autacoid release, receptor activation, and kinase cascades.

Main Results:

  • Identified both parallel and series signaling arrangements within cardiomyocytes.
  • Mapped the trigger phase involving adenosine, opioids, and bradykinin activating phosphatidylinositol 3-kinase (PI3-kinase) and extracellular signal regulated kinase (ERK).
  • Demonstrated nitric oxide, cyclic guanosine monophosphate (cGMP), protein kinase G (PKG), and protein kinase C (PKC) involvement, leading to mitochondrial radical generation and a persistent protected phenotype.

Conclusions:

  • The signaling map reveals distinct trigger and mediator phases.
  • Multiple signaling nodes, including PI3-kinase, ERK, and PKC, are critical for cardioprotection.
  • The findings identify numerous points for pharmacological intervention to induce cardioprotection.