Product Pathways - Protein Stability
ITCH (D8Q6D) Rabbit mAb #12117
|12117S||100 µl (10 western blots)||---||In Stock||---|
|12117||carrier free and custom formulation / quantity||email request|
Already purchased this product? Write a Review.
|W||1:1000||Human, Mouse, Rat||Endogenous||105||Rabbit IgG|
Species cross-reactivity is determined by western blot.
Applications Key: W=Western Blotting, IP=Immunoprecipitation
Specificity / Sensitivity
ITCH (D8Q6D) Rabbit mAb recognizes endogenous levels of total ITCH protein.
Source / Purification
Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Asp125 of human ITCH protein.
Western blot analysis of extracts from various cell lines using ITCH (D8Q6D) Rabbit mAb.
ITCH is a HECT domain-containing E3 ubiquitin ligase, first identified in genetic studies of the mouse agouti locus, in which mutations result in characteristic coat color changes. One particular agouti mutation (non-agouti-lethal 18H) is notable for the development of immunological defects not observed in other agouti mutant mice; these include lymphoid hyperplasia and chronic stomach, lung and skin inflammation (manifest as constant itching). The 18H agouti mutation was traced to a chromosomal inversion that disrupted expression of an adjacent gene in the agouti locus, subsequently termed Itch to reflect the chronic itching phenotype (1-3).
Further characterizations revealed that Itch encoded a NEDD4-like E3-ubiquitin ligase capable of catalyzing Lys29, Lys48, and/or Lys63-linked ubiquitination of target proteins, leading to their degradation by the proteosome pathway (4-6). The distinct phenotypes of Itch mutant mice led to the identification of an important regulatory role for ITCH-mediated ubiquitination in inflammatory signaling pathways. For example, ITCH-mediated ubiquitination of the transcription factor JunB was shown to play a direct inhibitory role in regulating expression of the proinflammatory cytokine IL-4. ITCH-null T lymphocytes consequently exhibit increased production of IL-4, leading to biased differentiation of naive CD4+ cells towards the proinflammatory Th2 lineage (7). In accordance with the findings from mutant Itch mouse models, a genetic linkage study in humans identified loss-of-function mutations in ITCH as a direct cause of syndromic multisystem autoimmune disease (SMAD) (8).
Notably, targets of ITCH-mediated ubiquitination are not restricted to immune signaling pathways. For example, key mediators of the Hedgehog (9,10), Wnt/β-catenin (11), Hippo (12), and Notch signaling pathways (13,14) have been identified as important targets of ITCH-mediated ubiquitination (2).
- Matesic, L.E. et al. (2008) Curr Top Microbiol Immunol 321, 185-200.
- Melino, G. et al. (2008) Cell Death Differ 15, 1103-12.
- Perry, W.L. et al. (1998) Nat Genet 18, 143-6.
- Chastagner, P. et al. (2006) EMBO Rep 7, 1147-53.
- Lee, T.L. et al. (2008) Biochem Biophys Res Commun 375, 326-30.
- Ahmed, N. et al. (2011) Nat Immunol 12, 1176-83.
- Fang, D. et al. (2002) Nat Immunol 3, 281-7.
- Lohr, N.J. et al. (2010) Am J Hum Genet 86, 447-53.
- Di Marcotullio, L. et al. (2006) Nat Cell Biol 8, 1415-23.
- Di Marcotullio, L. et al. (2011) Oncogene 30, 65-76.
- Wei, W. et al. (2012) Mol Cell Biol 32, 3903-12.
- Salah, Z. et al. (2011) Cancer Res 71, 2010-20.
- Qiu, L. et al. (2000) J Biol Chem 275, 35734-7.
- McGill, M.A. and McGlade, C.J. (2003) J Biol Chem 278, 23196-203.
Have you published research involving the use of our products? If so we'd love to hear about it. Please let us know!
- 7003 20X LumiGLO® Reagent and 20X Peroxide
- 7720 Prestained Protein Marker, Broad Range (Premixed Format)
- 7727 Biotinylated Protein Ladder Detection Pack
- 8480 β-Catenin (D10A8) XP® Rabbit mAb
- 3608 Notch1 (D1E11) XP® Rabbit mAb
- 4380 Notch1 (D6F11) XP® Rabbit mAb
- 4147 Cleaved Notch1 (Val1744) (D3B8) Rabbit mAb
- 9878 Phospho-Numb (Ser276) (D5C2) Rabbit mAb
- 2756 Numb (C29G11) Rabbit mAb
- 8053 Phospho-JunB (Thr102/Thr104) (D3C6) Rabbit mAb
- 3753 JunB (C37F9) Rabbit mAb
- 3477 LATS1 (C66B5) Rabbit mAb
- 8814 Non-phospho (Active) β-Catenin (Ser33/37/Thr41) (D13A1) Rabbit mAb
For Research Use Only. Not For Use In Diagnostic Procedures.
Cell Signaling Technology® is a trademark of Cell Signaling Technology, Inc.