Cell Signaling Technology

Product Pathways - Neuroscience

Phospho-AMPA Receptor (GluR 2) (Tyr876) Antibody #4027

Applications Reactivity Sensitivity MW (kDa) Source
W R (H) (M) Endogenous 100 Rabbit

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human  M=Mouse  R=Rat
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

Phospho-AMPA Receptor (GluR 2) (Tyr876) Antibody detects endogenous levels of GluR 2 only when phosphorylated at Tyr876. It may also detect GluR 3 when phosphorylated at the conserved Tyr887. This residue is not conserved in GluR 1 or GluR 4.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr876 of human GluR 2. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from rat brain, either sham-operated, 15 min ischemia followed by 4 h reperfusion or 15 min ischemia only, using Phospho-AMPA Receptor (GluR 2) (Tyr876) Antibody (upper) or AMPA Receptor (GluR 2/3/4) Antibody #2460 (lower).

Background

AMPA- (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), kainite-, and NMDA- (N-methyl-D-aspartate) receptors are the three main families of ionotropic glutamate-gated ion channels. AMPA receptors (AMPARs) are comprised of four subunits (GluR 1-4), which assemble as homo- or hetero-tetramers to mediate the majority of fast excitatory transmissions in the CNS. AMPARs are implicated in synapse formation, stabilization, and plasticity (1). AMPARs that lack GluR 2 are permeable to calcium, in contrast to GluR 2-containing AMPARs (2). Post-transcriptional modifications (alternative splicing, nuclear RNA editing) and post-translational modifications (glycosylation, phosphorylation) result in a very large number of permutations, fine-tuning the kinetic properties of AMPARs. Research studies have implicated activity changes in AMPARs in a variety of diseases including Alzheimer’s, amyotrophic lateral sclerosis (ALS), stroke, and epilepsy (1).

Src family tyrosine kinases phosphorylate the GluR 2 subunit of AMPA receptors at Tyr876, which increases the interaction with GRIP1/2 but not PICK1. In addition, Tyr876 is important for AMPA- and NMDA-induced GluR 2 internalization (3).The phosphorylation site at Tyr876 was also independently identified at Cell Signaling Technology (CST) using PhosphoScan®, CST's MS/MS platform for phosphorylation site discovery. Phosphorylation of GluR at Tyr876 was observed in extracts isolated from ischemic rat brain.

  1. Palmer, C.L. et al. (2005) Pharmacol Rev 57, 253-77.
  2. Cull-Candy, S. et al. (2006) Curr Opin Neurobiol 16, 288-97.
  3. Hayashi, T. and Huganir, R.L. (2004) J. Neurosci. 24, 6152-6160.

Application References

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

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