Related Experiment Video

Updated: May 17, 2026

Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

AMP-activated protein kinase: a target for drugs both ancient and modern

D Grahame Hardie1, Fiona A Ross, Simon A Hawley

  • 1Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK. d.g.hardie@dundee.ac.uk

Chemistry & Biology
|October 30, 2012
PubMed

Insights

AMP-activated protein kinase (AMPK) senses cellular energy. AMPK activators, like metformin and aspirin, show potential for treating type 2 diabetes and cancer by regulating metabolic pathways.

Area of Science:

  • Biochemistry
  • Cellular Metabolism
  • Pharmacology

Background:

  • AMP-activated protein kinase (AMPK) functions as a critical sensor of cellular energy levels.
  • AMPK activation is triggered by metabolic stresses that alter cellular adenine nucleotide ratios (ADP:ATP, AMP:ATP).
  • Activation requires the tumor suppressor LKB1 and modulates ATP-generating catabolic pathways while inhibiting ATP-consuming biosynthetic pathways and cell-cycle progression.

Purpose of the Study:

  • To review the mechanisms of AMPK activation.
  • To explore the therapeutic potential of AMPK activators in type 2 diabetes and cancer.
  • To discuss activation by drugs and natural products.

Main Methods:

  • Literature review of AMPK activation mechanisms.
  • Analysis of drug-induced AMPK activation (metformin, salicylate).
  • Examination of natural product effects on AMPK.

Main Results:

  • AMPK activation by metformin (diabetes treatment) and salicylate (aspirin metabolite) is established.
  • Epidemiological data suggest metformin and aspirin may offer protection against cancer.
  • Various drugs and natural products can activate AMPK.

Conclusions:

  • AMPK activators hold promise for type 2 diabetes and cancer treatment/prevention.
  • Understanding AMPK activation mechanisms is key to developing novel therapeutics.
  • Metformin, aspirin, and certain natural products represent viable AMPK-targeting agents.

More Related Videos

Assaying Protein Kinase Activity with Radiolabeled ATP08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-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,...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...