Datasheet

Biological Description

Specificity	AMPKγ1 Antibody [M8F13] detects endogenous levels of total AMPKγ1 protein.
Background	AMPKγ1, also known as PRKAG1, is the regulatory gamma subunit of AMP-activated protein kinase (AMPK), a heterotrimeric energy sensor complex composed of alpha catalytic and beta scaffold subunits. This protein contains three canonical cystathionine-β-synthase (CBS) domains, which pair to form four adenine nucleotide-binding sites. The first CBS domain houses a binding site with key arginine and histidine residues that are critical for AMP and ATP coordination. An N-terminal extension and the second CBS domain link the structure, while a C-terminal tail helps stabilize the assembly of the heterotrimer. When AMP binds to its primary site, AMPKγ1 undergoes conformational changes that expose the activation loop (T-loop) on the alpha subunit, allowing phosphorylation by upstream kinases such as LKB1 and CaMKKβ. This modification amplifies AMPK’s kinase activity dramatically and protects it from dephosphorylation by protein phosphatases. ADP binding at alternative sites provides moderate activation, whereas ATP binding inhibits the enzyme through intrasteric occlusion. Activated AMPK phosphorylates key metabolic targets, including ACC and HMGCR, to suppress lipid and cholesterol synthesis, and TSC2 to limit anabolic processes. It simultaneously promotes catabolic pathways by activating PGC1α and ULK1 for mitochondrial biogenesis and autophagy, increasing glucose uptake via GLUT4 translocation, and restraining gluconeogenesis through FOXO signaling. AMPK also influences cell polarity by remodeling actin structures through phosphorylation of myosin light chain kinase and cofilin. Isoform specificity is notable: the γ1 subunit is predominant in hepatocytes and the liver, where it is crucial for mediating the effects of metformin, particularly through its CBS domains. Loss of γ1 abolishes activation loop phosphorylation and disrupts glucose-suppressing effects. In animal models, the absence of γ1 impairs the anti-hyperglycemic action of metformin under high-fat diets. Mutations that disrupt AMP binding, such as substitutions at critical arginine residues, can mimic cardiac pathologies seen with other AMPK gamma isoforms, including Wolff-Parkinson-White syndrome. In cancer, tumor cells may take advantage of constitutive AMPK activity for survival under metabolic stress, while silencing γ1 impairs proliferation in such conditions. Defective hepatic γ1 function in diabetes leads to elevated glucose output and impaired metabolic regulation.

Specificity

AMPKγ1 Antibody [M8F13] detects endogenous levels of total AMPKγ1 protein.

Background

AMPKγ1, also known as PRKAG1, is the regulatory gamma subunit of AMP-activated protein kinase (AMPK), a heterotrimeric energy sensor complex composed of alpha catalytic and beta scaffold subunits. This protein contains three canonical cystathionine-β-synthase (CBS) domains, which pair to form four adenine nucleotide-binding sites. The first CBS domain houses a binding site with key arginine and histidine residues that are critical for AMP and ATP coordination. An N-terminal extension and the second CBS domain link the structure, while a C-terminal tail helps stabilize the assembly of the heterotrimer. When AMP binds to its primary site, AMPKγ1 undergoes conformational changes that expose the activation loop (T-loop) on the alpha subunit, allowing phosphorylation by upstream kinases such as LKB1 and CaMKKβ. This modification amplifies AMPK’s kinase activity dramatically and protects it from dephosphorylation by protein phosphatases. ADP binding at alternative sites provides moderate activation, whereas ATP binding inhibits the enzyme through intrasteric occlusion. Activated AMPK phosphorylates key metabolic targets, including ACC and HMGCR, to suppress lipid and cholesterol synthesis, and TSC2 to limit anabolic processes. It simultaneously promotes catabolic pathways by activating PGC1α and ULK1 for mitochondrial biogenesis and autophagy, increasing glucose uptake via GLUT4 translocation, and restraining gluconeogenesis through FOXO signaling. AMPK also influences cell polarity by remodeling actin structures through phosphorylation of myosin light chain kinase and cofilin. Isoform specificity is notable: the γ1 subunit is predominant in hepatocytes and the liver, where it is crucial for mediating the effects of metformin, particularly through its CBS domains. Loss of γ1 abolishes activation loop phosphorylation and disrupts glucose-suppressing effects. In animal models, the absence of γ1 impairs the anti-hyperglycemic action of metformin under high-fat diets. Mutations that disrupt AMP binding, such as substitutions at critical arginine residues, can mimic cardiac pathologies seen with other AMPK gamma isoforms, including Wolff-Parkinson-White syndrome. In cancer, tumor cells may take advantage of constitutive AMPK activity for survival under metabolic stress, while silencing γ1 impairs proliferation in such conditions. Defective hepatic γ1 function in diabetes leads to elevated glucose output and impaired metabolic regulation.

Usage Information

Application

WB, IP, FCM

Dilution

WB	IP	FCM
1:1000 – 1:10000	1:100	1:100

Reactivity

Human

Source

Rabbit Monoclonal Antibody

MW

38 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/30423971/
https://pubmed.ncbi.nlm.nih.gov/17452784/

AMPKγ1 Antibody [M8F13]

Biological Description

Usage Information

References

Application Data