Cell Signaling Technology
XP Monoclonal Antibody

Product Pathways - PI3K / Akt Signaling

GSK-3α (D80D1) XP® Rabbit mAb #4818

Applications Reactivity Sensitivity MW (kDa) Isotype
IF-IC F H M (R) Endogenous 51 Rabbit IgG

Applications Key:  IF-IC=Immunofluorescence (Immunocytochemistry)  F=Flow Cytometry
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

GSK-3α (D80D1) XP® Rabbit mAb detects endogenous levels of total GSK-3α protein. The antibody does not cross-react with GSK-3β.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to the sequence of human GSK-3α.

Flow Cytometry

Flow Cytometry

Flow cytometric analysis of MEF/GSK-3β (-/-) cells (red), MEF/GSK-3α (-/-) cells (green), and MEF/GSK-3 wildtype cells (blue) using GSK-3α (D80D1) XP® Rabbit mAb. (MEF/GSK-3 wildtype, GSK-3α (-/-) and GSK-3β (-/-) cells were kindly provided by Dr. Jim Woodgett, University of Toronto, Canada).

IF-IC

IF-IC

Confocal immunofluorescent analysis of MEF/GSK-3 wildtype cells (left), MEF/GSK-3β (-/-) cells (center) and MEF/GSK-3α (-/-) cells (right), using GSK-3α (D80D1) XP® Rabbit mAb (green). Actin filaments have been labeled with DY-554 phalloidin (red). Blue pseudocolor = DRAQ5® #4084 (fluorescent DNA dye). (MEF/wildtype, GSK-3α (-/-) and GSK-3β (-/-) cells were kindly provided by Dr. Jim Woodgett, University of Toronto, Canada).

Background

Glycogen synthase kinase-3 (GSK-3) was initially identified as an enzyme that regulates glycogen synthesis in response to insulin (1). GSK-3 is a ubiquitously expressed serine/threonine protein kinase that phosphorylates and inactivates glycogen synthase. GSK-3 is a critical downstream element of the PI3K/Akt cell survival pathway whose activity can be inhibited by Akt-mediated phosphorylation at Ser21 of GSK-3α and Ser9 of GSK-3β (2,3). GSK-3 has been implicated in the regulation of cell fate in Dictyostelium and is a component of the Wnt signaling pathway required for Drosophila, Xenopus, and mammalian development (4). GSK-3 has been shown to regulate cyclin D1 proteolysis and subcellular localization (5).

GSK-3α regulates the production of amyloid-β peptides, a major component of the plaques that accumulate with progression of Alzheimer disease. Administration of therapeutic concentrations of lithium, a GSK-3 inhibitor, attenuates amyloid-β production by specifically inhibiting the cleavage of amyloid precursor protein (APP) by γ-secretase, blocking accumulation of amyloid-β peptides in the brains of mice that overproduce APP (6).

  1. Welsh, G.I. et al. (1996) Trends Cell. Biol. 6, 274-279.
  2. Srivastava, A.K. and Pandey, S.K. (1998) Mol. Cell. Biochem. 182, 135-141.
  3. Cross, D.A. et al. (1995) Nature 378, 785-789.
  4. Nusse, R. (1997) Cell 89, 321-323.
  5. Diehl, J.A. et al. (1998) Genes Dev. 12, 3499-3511.
  6. Phiel, C.J. et al. (2003) Nature 423, 435-9.

Application References

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This product is intended for research purposes only. The product is not intended to be used for therapeutic or diagnostic purposes in humans or animals.

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