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Products >  Inducible_Systems >  Protein-Protein_Interactions >  Homodimer

iDimerize Inducible Homodimer System

The iDimerize Inducible Homodimer System brings protein-protein interactions under real-time, small molecule control. A protein of interest is fused to the DmrB binding domain, and dimerization is induced by adding the B/B Homodimerizer (AP20187). This cell-permeable ligand induces two or more copies of the DmrB fusion protein to interact. iDimerize Inducible Homodimer technology has been used to create conditional alleles of cell surface receptors, signaling molecules, and other proteins which are regulated by protein-protein interactions. Induced protein homodimerization is already widely used in vitro and in vivo to control signaling pathways, and it can be used to induce any type of event that is activated or controlled by protein-protein interactions, including proliferation, differentiation, adhesion, transformation, and apoptosis. Plasmid and lentiviral (Lenti-X) vector formats are available.

Note: While it is possible to use the iDimerize Inducible Homodimer System to induce heterodimerization, you will obtain a mixture of homodimers and heterodimers. To induce heterodimers specifically and exclusively, use the iDimerize Inducible Heterodimer System.

B/B Homodimerizer Ligand (AP20187)

The B/B Homodimerizer is a synthetic, cell-permeable ligand that can be used to induce homodimerization of fusion proteins containing the DmrB domain. It is nontoxic in vitro and in mice (recommended dosage range, 0.01–100 nM for in vitro use or 0.005–10 mg/kg in mice). The B/B Homodimerizer is identical to the AP20187 ligand, which was previously supplied by ARIAD Pharmaceuticals Inc.

B/B Washout Ligand

B/B Washout Ligand dissociates protein interactions that were induced by the B/B Homodimerizer (T1/2 ~10 minutes). The B/B Washout Ligand has a much greater effect on target cells that have been treated with B/B Homodimerizer than simply replacing medium containing B/B Homodimerizer with medium without B/B Homodimerizer.

iDimerize Inducible Homodimer Systems (with Tet-On 3G)

One challenge of ligand-dependent dimerization experiments is that non ligand-induced dimerization events may occur if the protein of interest is expressed at high levels. This is especially problematic if the target protein is a membrane protein, because the local concentration can increase quickly due to the limited space on the membrane. We’ve combined iDimerize and Tet-On 3G technologies to eliminate these unwanted events. First, use doxycycline to optimize the protein's expression to physiologically-relevant levels. Then induce dimerization by adding the dimerizer ligand to your culture medium.

Application: Signal Transduction

Many signaling cascades are activated almost exclusively by the interactions of signaling proteins. Cell surface receptor proteins cluster in response to extracellular factors, which leads to the recruitment and activation of intracellular signaling proteins, transcription activation, effector protein production, and finally to protein activation or secretion. Any step of this signaling pathway that relies on a dimerization event can be brought under dimerizer control by fusing the proteins involved to the DmrB domain.

Example 1: Inducing a Programmed Cell Death Pathway (Inducible Apoptosis)
The Fas receptor (FasR) is a transmembrane protein located on the surface of cells that activates programmed cell death (apoptosis) when induced to trimerize by fas ligand (FasL) molecules located on the surface of adjacent cells (e.g., cytotoxic T cells). FasR-FasL binding plays an important role in the regulation of the immune system and cancer progression. This trimerization (and the resulting apoptotic signaling cascade) can be mimicked using the iDimerize Inducible Homodimer System: cells expressing a FasR-DmrB fusion protein can induce cell death on demand, simply by adding the B/B Homodimerizer. An in vivo model (the MaFIA mouse; 1) utilizes the Fas receptor to systematically and reversibly eliminate macrophages from transgenic mice.

Example 2: Inducible Mouse Model for Prostate Cancer
iDimerize Inducible Homodimer technology was used to characterize the role of different FGF receptor subtypes (FGFR1 and FGFR2) in prostate cancer. Transgenic mice (which express conditionally active alleles of FGFR1 or FGFR2 in prostate tissue) were treated with B/B Homodimerizer and monitored for prostate cancer. FGFR1, but not FGFR2, was found to play a role in prostate cancer development (2).

At-A-Glance Documents Images & Data Resources

Features

  • Previously available from ARIAD as the ARGENT Regulated Homodimerization Kit
  • Rapid, chemical induction of cell signaling pathways
  • Activate any pathway or cellular event controlled by homooligomers (e.g. dimers, trimers, or tetramers)
  • Established tool used by over 2,000 research groups, with over 400 scientific publications to date
  • B/B Homodimerizer is identical to the AP20187 ligand
  • B/B Washout Ligand reverses protein oligomers that were induced by the B/B Homodimerizer
  • Plasmid and lentiviral (Lenti-X) vector formats are available

Applications

  • Induce any event or pathway that is controlled or activated by protein-protein interactions
  • Activate signaling pathways in real time
  • Study transmembrane receptors
  • Recruit signaling proteins to specific subcellular locations (e.g. the plasma membrane)
  • Inducible homodimer technology has been used for functional studies of:
    • Receptor and non-receptor tyrosine kinases
    • Receptor and non-receptor serine/threonine kinases
    • Non-kinase receptors
    • Signaling proteases
    • Adaptor proteins
    • Cell adhesion and rolling
    • DNA looping
    • Activation of recombinase
    • RNA splicing
    • Protein splicing
    • Glycosylation

References

  1. Burnett, S. H. et al. (2004) J. Leukoc. Biol. 75(4):612–623. Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene.
  2. Freeman, K. W. et al. (2003) Cancer Res. 63(23):8256–8563. Inducible prostate intraepithelial neoplasia with reversible hyperplasia in conditional FGFR1-expressing mice.

Additional Information

Please see the product's Certificate of Analysis for information about storage conditions, product components, and technical specifications. Please see the Kit Components List to determine kit components. Certificates of Analysis and Kit Components Lists are located under the Documents tab.


 
 
Products
Cat. # Product Package Size Price License # of Units Select
635058 B/B Homodimerizer 5 mg $2,442.00 License Statements
635060 B/B Homodimerizer 500 uL $352.00 License Statements
635059 B/B Homodimerizer 5 x 500 uL $1,397.00 License Statements
635069 B/B Homodimerizer 25 mg $6,654.00 License Statements
635088 B/B Washout Ligand 500 uL $352.00 License Statements
635072 Lenti-X™ iDimerize™ Inducible Homodimer System Each $1,195.00 License Statements
635086 Lenti-X™ iDimerize™ Inducible Homodimer System (with Tet-On® 3G) Each $1,768.00 License Statements *
635068 iDimerize™ Inducible Homodimer System Each $1,095.00 License Statements
635084 iDimerize™ Inducible Homodimer System (with Tet-On® 3G) Each $1,195.00 License Statements *
 
* You must log in if you would like to purchase these products online, since the purchase of these products may be restricted depending on your account type. Researchers at not-for-profit accounts receive a limited use license with their purchase of the product. Researchers at for-profit accounts must obtain a license prior to purchase. For details please contact licensing@clontech.com.

 

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