Related Experiment Video

Updated: Jul 13, 2026

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation
09:04

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation

Published on: September 7, 2010

Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation

N A Clipstone1, G R Crabtree

  • 1Beckman Center for Molecular and Genetic Medicine, Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305.

Nature
|June 25, 1992
PubMed

Insights

Overexpressing calcineurin in T-cells makes them resistant to immunosuppressive drugs like cyclosporin A (CsA) and FK506. This finding reveals calcineurin

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Cyclosporin A (CsA) and FK506 are immunosuppressive drugs impacting T-cell activation.
  • These drugs interfere with calcium-dependent signaling pathways crucial for lymphokine gene expression.
  • CsA and FK506 bind intracellular receptors, cyclophilin and FKBP, respectively.

Purpose of the Study:

  • To investigate the role of calcineurin in the mechanism of action of CsA and FK506.
  • To test the hypothesis that calcineurin interaction with drug-receptor complexes mediates immunosuppression.

Main Methods:

  • Overexpression of calcineurin in Jurkat T-cells.
  • Assessing cellular resistance to CsA and FK506.
  • Measuring NFAT- and NF-IL2A-dependent transcription.

Main Results:

  • Calcineurin overexpression conferred resistance to CsA and FK506 in Jurkat cells.
  • Enhanced calcineurin activity augmented NFAT- and NF-IL2A-dependent transcription.
  • Demonstrated a direct link between calcineurin activity and drug response.

Conclusions:

  • Calcineurin is a critical enzyme in T-cell signal transduction.
  • Drug-isomerase complex interaction with calcineurin is the molecular basis for CsA/FK506 immunosuppression.
  • Provides biological evidence supporting calcineurin's role in immunosuppressive drug efficacy.

More Related Videos

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes09:14

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes

Published on: June 13, 2014

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells09:04

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

Related Concept Videos

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...