Cell Signaling Technology

Product Pathways - Protein Stability

ITCH (D8Q6D) Rabbit mAb #12117

Itchy   NFE2-associated   sc-25625  

No. Size Price
12117S 100 µl ( 10 western blots ) ¥3,250.00 现货查询 购买询价
12117 carrier free & custom formulation / quantityemail request
Applications Dilution Species-Reactivity Sensitivity MW (kDa) Isotype
W 1:1000 Human,Mouse,Rat, Endogenous 105 Rabbit IgG
IP 1:200

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.

ITCH (D8Q6D) Rabbit mAb兔单抗识别内源性的ITCH总蛋白。

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Asp125 of human ITCH protein.


Western Blotting

Western Blotting

Western blot analysis of extracts from various cell lines using ITCH (D8Q6D) Rabbit mAb. Western blot检测多种细胞提取物。



Immunoprecipitation of ITCH from MOLT-4 cell extracts using Rabbit (DA1E) mAb IgG XP® Isotype Control #3900 (lane 2) or ITCH (D8Q6D) Rabbit mAb (lane 3). Lane 1 is 10% input. Western blot analysis was performed using ITCH (D8Q6D) Rabbit mAb. Western blot采用Rabbit (DA1E) mAb IgG XP® 同型对照#3900 (lane 2) 或 ITCH (D8Q6D) Rabbit mAb (lane 3)检测MOLT-4细胞提取物中ITCH。Lane 1中样品浓度为10%。


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).

ITCH是一种包含有HECT结构域的E3泛素连接酶,首先在小鼠agouti基因的研究中发现,其突变可导致皮毛的颜色改变。一种特殊的agouti (non-agouti-lethal 18H)基因突变对于免疫缺陷的发育至关重要,在其他agouti基因突变的小鼠包括淋巴样增生和慢性胃、肺和皮肤炎症(已证实持续瘙痒)中并未发现。18H agouti突变是由于染色体倒位,破坏了agouti基因中临近基因的表达,随后命名为Itch以反映慢性的itching表型(1-3)。进一步的特征表明,Itch编码NEDD4-like E3-泛素连接酶,其能够催化与Lys29, Lys48, 和/或 Lys63-结合的靶向蛋白的泛素化作用,从而进入蛋白体途径的降解(4-6)。Itch突变小鼠的不同的表型对炎症信号通路中ITCH-介导的泛素化作用发挥重要的调节作用。例如,ITCH-介导转录因子JunB的泛素化作用,被证实在致炎细胞因子IL-4的表达调节中起直接的抑制作用。因此,无ITCH的T淋巴细胞中,IL-4的产生增多,进而导致初始CD4+细胞的偏向Th2谱系致炎细胞因子的分化(7)。与Itch突变的鼠模型一样,人连锁研究表明,ITCH突变导致的功能丧失直接导致了综合的多系统自身免疫性疾病(SMAD) (8)。值得注意的是,ITCH-介导的泛素化作用的靶点并不局限于免疫信号通路。例如,Hedgehog (9,10), Wnt/β-catenin (11), Hippo (12), 和Notch信号通路(13,14)的主要介导者被确定是ITCH-介导泛素化作用的重要靶点(2)。

  1. Matesic, L.E. et al. (2008) Curr Top Microbiol Immunol 321, 185-200.
  2. Melino, G. et al. (2008) Cell Death Differ 15, 1103-12.
  3. Perry, W.L. et al. (1998) Nat Genet 18, 143-6.
  4. Chastagner, P. et al. (2006) EMBO Rep 7, 1147-53.
  5. Lee, T.L. et al. (2008) Biochem Biophys Res Commun 375, 326-30.
  6. Ahmed, N. et al. (2011) Nat Immunol 12, 1176-83.
  7. Fang, D. et al. (2002) Nat Immunol 3, 281-7.
  8. Lohr, N.J. et al. (2010) Am J Hum Genet 86, 447-53.
  9. Di Marcotullio, L. et al. (2006) Nat Cell Biol 8, 1415-23.
  10. Di Marcotullio, L. et al. (2011) Oncogene 30, 65-76.
  11. Wei, W. et al. (2012) Mol Cell Biol 32, 3903-12.
  12. Salah, Z. et al. (2011) Cancer Res 71, 2010-20.
  13. Qiu, L. et al. (2000) J Biol Chem 275, 35734-7.
  14. McGill, M.A. and McGlade, C.J. (2003) J Biol Chem 278, 23196-203.

Application References

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