Related Experiment Video
Updated: May 30, 2026
08:05
Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
AMP-activated protein kinase: also regulated by ADP?
D Grahame Hardie1, David Carling, Steven J Gamblin
1College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK. d.g.hardie@dundee.ac.uk
Trends in Biochemical Sciences
|July 26, 2011
Summary
AMP-activated protein kinase (AMPK) regulates cellular energy. It is activated by ADP and AMP, preventing inactivation and maintaining energy homeostasis, with roles in starvation response and drug activation.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Regulation
Background:
- AMPK is a key energy sensor in eukaryotic cells.
- It responds to cellular stresses like ATP depletion.
- Its ancestral role involves regulating responses to carbon source starvation.
Purpose of the Study:
- To review recent findings on AMPK activation mechanisms.
- To discuss the role of ADP and AMP in AMPK activation.
- To explore the function of the β subunit's carbohydrate-binding module and drug-induced activation.
Main Methods:
- Literature review of recent findings on AMPK.
- Analysis of nucleotide binding mechanisms (ADP/AMP).
- Discussion of xenobiotic interactions with AMPK.
Main Results:
- AMPK activation is influenced by both AMP and ADP.
- Nucleotide binding to AMPK prevents its dephosphorylation and inactivation.
- The carbohydrate-binding module on the β subunit plays a role in AMPK regulation.
- Drugs like metformin and resveratrol activate AMPK through specific mechanisms.
Conclusions:
- AMPK activation is a complex process involving nucleotide binding and subunit interactions.
- Understanding AMPK regulation is crucial for metabolic homeostasis.
- AMPK serves as a target for therapeutic interventions in metabolic diseases.
Related Concept Videos
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:15Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...