Phospho-GSK3β (Y216)/GSK3α (Y279) Antibody [F22P22] Datasheet

Biological Description

Specificity	Phospho-GSK3β (Y216)/GSK3α (Y279) Antibody [F22P22] detects endogenous levels of total GSK3β and GSK3α protein only when it is phosphorylated at Y216 and Y279 respectively.
Background	Phosphorylated GSK3β (Y216) and GSK3α (Y279) denote activation‑loop tyrosine phosphorylation events on the two closely related glycogen synthase kinase 3 isoforms, which are constitutively active serine/threonine kinases that regulate multiple signaling cascades in the brain, liver, and other tissues. GSK3α and GSK3β both contain an N‑terminal kinase domain with a T‑loop whose phosphorylation at Y279 and Y216, respectively, stabilizes an open, active conformation that enhances substrate recognition and phosphotransfer to key effectors such as β‑catenin, glycogen synthase, and Tau. In the Wnt/β‑catenin pathway, active GSK3α and GSK3β phosphorylate β‑catenin within the destruction complex, promoting its ubiquitination and proteasomal degradation unless upstream Wnt ligands inhibit the complex through Dishevelled‑ and Axin‑dependent mechanisms, whereas in the insulin/PI3K/Akt axis Akt‑dependent inhibitory phosphorylation at Ser21 in GSK3α and Ser9 in GSK3β acts as a negative feedback node that dampens GSK3 activity and licenses glycogen synthase activation and normalized glucose metabolism. Phospho‑GSK3β (Y216)‑enriched states correlate with increased phosphorylation of Tau at multiple sites, contributing to Tau misfolding, tangle‑like assembly, and synaptic dysfunction in Alzheimer’s disease, while in metabolic tissues elevated GSK3β (Y216) phosphorylation is associated with impaired insulin signaling through IRS1, reduced glycogen synthesis, and dysglycemia in diabetes mellitus.

Specificity

Phospho-GSK3β (Y216)/GSK3α (Y279) Antibody [F22P22] detects endogenous levels of total GSK3β and GSK3α protein only when it is phosphorylated at Y216 and Y279 respectively.

Background

Phosphorylated GSK3β (Y216) and GSK3α (Y279) denote activation‑loop tyrosine phosphorylation events on the two closely related glycogen synthase kinase 3 isoforms, which are constitutively active serine/threonine kinases that regulate multiple signaling cascades in the brain, liver, and other tissues. GSK3α and GSK3β both contain an N‑terminal kinase domain with a T‑loop whose phosphorylation at Y279 and Y216, respectively, stabilizes an open, active conformation that enhances substrate recognition and phosphotransfer to key effectors such as β‑catenin, glycogen synthase, and Tau. In the Wnt/β‑catenin pathway, active GSK3α and GSK3β phosphorylate β‑catenin within the destruction complex, promoting its ubiquitination and proteasomal degradation unless upstream Wnt ligands inhibit the complex through Dishevelled‑ and Axin‑dependent mechanisms, whereas in the insulin/PI3K/Akt axis Akt‑dependent inhibitory phosphorylation at Ser21 in GSK3α and Ser9 in GSK3β acts as a negative feedback node that dampens GSK3 activity and licenses glycogen synthase activation and normalized glucose metabolism. Phospho‑GSK3β (Y216)‑enriched states correlate with increased phosphorylation of Tau at multiple sites, contributing to Tau misfolding, tangle‑like assembly, and synaptic dysfunction in Alzheimer’s disease, while in metabolic tissues elevated GSK3β (Y216) phosphorylation is associated with impaired insulin signaling through IRS1, reduced glycogen synthesis, and dysglycemia in diabetes mellitus.

Usage Information

Application

WB, IP, IHC

Dilution

WB	IP	IHC
1:500-1:2000	1:40	1:50

Reactivity

Rat, Human, Zebrafish, Mouse

Source

Rabbit Monoclonal Antibody

MW

50 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/31057171/
https://pubmed.ncbi.nlm.nih.gov/38882600/

Application Data

WB

Validated by Selleck

Lane 1: PC12, Lane 2: PC12 (nerve growth factor-β, 100ng/ml, 5 min), Lane 3: PC12 (nerve growth factor-β, 100ng/ml, 5 min; phosphatase treated), Lane 4: Mouse brain