Cell Signaling Technology
XP Monoclonal Antibody

Product Pathways - Cytoskeletal Signaling

APPL1 (D83H4) XP® Rabbit mAb #3858

Applications Reactivity Sensitivity MW (kDa) Isotype
W IP IF-IC H M R Mk Endogenous 82 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation  IF-IC=Immunofluorescence (Immunocytochemistry)
Reactivity Key:  H=Human  M=Mouse  R=Rat  Mk=Monkey
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

APPL1 (D83H4) XP® Rabbit mAb detects endogenous levels of total APPL1 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Thr426 of human APPL1.

Western Blotting

Western Blotting

Western blot analysis of extracts from various cell types using APPL1 (D83H4) XP® Rabbit mAb.

IF-IC

IF-IC

Confocal immunofluorescent analysis of HeLa cells using APPL1 (D83H4) XP® Rabbit mAb (green). Blue pseudocolor = DRAQ5® #4084 (fluorescent DNA dye).

Background

The APPL1 multidomain adaptor protein is a BAR-domain protein family member that is involved in membrane trafficking within a number of signal transduction pathways (1). The amino-terminal BAR domain mediates the formation of crescent-shaped APPL1 homodimers (or APPL1 and APPL2 heterodimers) important to lipid binding and membrane curvature sensing (1). The PH domain of APPL1 is required for binding of the adaptor protein to Rab5 GTPase (2). In response to extracellular stimuli, Rab5 GTP hydrolysis releases APPL1 from the endosome and allows translocation of APPL1 to the nucleus where it joins a protein complex that controls chromatin remodeling and gene expression (3). The carboxy-terminal PTB domain of APPL1 enables an interaction between APPL1 and the TrkA neurotrophin receptor. An association between these two proteins and the TrkA-interacting protein GIPC1 within endosomes is required for nerve growth factor mediated signaling (4). APPL1 also binds follicle-stimulating hormone (FSH) receptors, which may provide a relay of FSH signaling to the PI3K/Akt pathway (5). The APPL1 adaptor protein is implicated in insulin signaling, as interaction between APPL1 and Akt2 is required for insulin-stimulated translocation of GLUT4 receptor proteins. Both induced overexpression and knockdown of APPL1 inhibit insulin-stimulated GLUT4 translocation (6). APPL1 binds the adiponectin receptor and acts as a downstream effector in the adiponectin pathway to mediate NO production (7,8). APPL1 interacts with DCC (deleted in colorectal cancer) protein and may play a role in DCC-induced apoptosis (9).

  1. Habermann, B. (2004) EMBO Rep 5, 250-5.
  2. Zhu, G. et al. (2007) EMBO J 26, 3484-93.
  3. Miaczynska, M. et al. (2004) Cell 116, 445-56.
  4. Lin, D.C. et al. (2006) Mol Cell Biol 26, 8928-41.
  5. Nechamen, C.A. et al. (2004) Biol Reprod 71, 629-36.
  6. Saito, T. et al. (2007) J Biol Chem 282, 32280-7.
  7. Mao, X. et al. (2006) Nat Cell Biol 8, 516-23.
  8. Cheng, K.K. et al. (2007) Diabetes 56, 1387-94.
  9. Liu, J. et al. (2002) J Biol Chem 277, 26281-5.

Application References

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Companion Products

For Research Use Only. Not For Use In Diagnostic Procedures.

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