Glycogen Synthase Kinase 3 alpha, CT (GSK 3 alpha, GSK3alpha, GSK-3 alpha, GSK 3A, GSK3a, DKFZp686D0638)

Glycogen synthase kinase 3-alpha (GSK3A)is a multifunctional protein serine kinase implicated in the control of several regulatory proteins including glycogen synthase and transcription factors. It also plays a role in the WNT and PI3K signaling pathways. Under resting conditions GSK3A and its homologs are highly phosphorylated at tyr279 in the phosphorylation loop. Constitutive phosphorylation of this tyrosine is important for kinase activity. Dephosphorylation of tyr279 after mitogen activation is accompanied by kinase inactivation. PKA as well as PI3K-activated PKB inactivate GSK3A by phosphorylation at ser21 Lysophosphatidic acid primarily utilizes a PKC-dependent pathway to modulate GSK3 and certain growth factors (e.g., PDGFB), which control GSK3 mainly through PIK3-PKB, are able to regulate GSK3 through an alternative, redundant phospholipase-C-gamma-PKC pathway.4 Alzheimer disease (AD) is associated with increased production and aggregation of amyloid-beta-40 and -42 peptides into plaques. GSK3A is required for maximal production of the beta-amyloid-40 and -42 peptides generated from the amyloid precursor protein (APP) by presenilin (PSEN1)-dependent gamma-secretase cleavage. In vitro, lithium, a GSK3A inhibitor, blocked the production of the beta-amyloid peptides by interfering with the gamma-secretase step. In mice expressing familial AD-associated mutations in APP and PSEN1, lithium reduced the levels of beta-amyloid peptides GSK3A also phosphorylates the tau protein (MAPT), the principal component of neurofibrillary tangles in AD, and suggested that inhibition of GSK3A may offer a new therapeutic approach to AD.\n\nApplications: \nSuitable for use in ELISA, Western Blot, and Immunohistochemistry. Other applications not tested.\n\nRecommended Dilution:\nELISA: 1:1,000\nWestern Blot: 1:100-1:500\nImmunohistochemistry: 1:50-1:100\nOptimal dilutions to be determined by the researcher.\n\nStorage and Stability:\nMay be stored at 4 degrees C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Aliquots are stable for at least 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.

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