Molecule Information

General Information of the Molecule (ID: Mol04010)

• Name: AMP-activated protein kinase (AMPK) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: PRKAB2
• Gene ID: 5565
• Location: chr1:147155106-147172550[-]
• Sequence:
  MGNTTSDRVSGERHGAKAARSEGAGGHAPGKEHKIMVGSTDDPSVFSLPDSKLPGDKEFV
  SWQQDLEDSVKPTQQARPTVIRWSEGGKEVFISGSFNNWSTKIPLIKSHNDFVAILDLPE
  GEHQYKFFVDGQWVHDPSEPVVTSQLGTINNLIHVKKSDFEVFDALKLDSMESSETSCRD
  LSSSPPGPYGQEMYAFRSEERFKSPPILPPHLLQVILNKDTNISCDPALLPEPNHVMLNH
  LYALSIKDSVMVLSATHRYKKKYVTTLLYKPI
• 3D-structure: PDB ID: 7JHG; Classification: Transferase/immune system; Method: Electron microscopy; Resolution: 3.47 Å
• Function: Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C- terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
• Uniprot ID: AAKB2_HUMAN
• Ensembl ID: ENSG00000131791
• HGNC ID: HGNC:9379

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Metformin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Squamous cell carcinoma [ICD-11: 2C31.0] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Squamous cell carcinoma [ICD-11: 2C31.0]
• Sensitive Drug: Metformin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: mTOR signaling pathway; Activation; hsa04150
• Cell Pathway Regulation: Insulin signaling pathway; Activation; hsa04910
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: PDT resistant cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: SCC13 cells; Skin; Homo sapiens (Human); CVCL_4029
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Our results reveal that PDT resistance implies, at least partially, a metabolic reprogramming towards aerobic glycolysis that is prevented by metformin treatment. Therefore, metformin may constitute an excellent adjuvant for PDT in sSCC.

Disease Class: Squamous cell carcinoma [ICD-11: 2C31.0] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Squamous cell carcinoma [ICD-11: 2C31.0]
• Sensitive Drug: Metformin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: mTOR signaling pathway; Activation; hsa04150
• Cell Pathway Regulation: Insulin signaling pathway; Activation; hsa04910
• In Vivo Model: Nude mice, 10GT SCC13 cells; nude mice, PDT. P cells; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Our results reveal that PDT resistance implies, at least partially, a metabolic reprogramming towards aerobic glycolysis that is prevented by metformin treatment. Therefore, metformin may constitute an excellent adjuvant for PDT in sSCC.

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [2]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Sorafenib
• Molecule Alteration: Activity; activation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh7-AMPKAR2 cells; Liver; Homo sapiens (Human); CVCL_0336
• Experiment for Molecule Alteration: FRET-based high content imaging
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Our findings suggest that glycolysis promotes sorafenib resistance through maintaining AMPK activation.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [2]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Sensitive Drug: Sorafenib
• Molecule Alteration: Activity; inhibit
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh7-AMPKAR2 cells; Liver; Homo sapiens (Human); CVCL_0336
• Experiment for Molecule Alteration: FRET-based high content imaging
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Our findings suggest that glycolysis promotes sorafenib resistance through maintaining AMPK activation.

References

• Ref 1: Metformin overcomes metabolic reprogramming-induced resistance of skin squamous cell carcinoma to photodynamic therapy. Mol Metab. 2022 Jun;60:101496.
• Ref 2: Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect. Mol Metab. 2023 Nov;77:101796.