AK2 Mouse
Description
Global AK2 Knockout (AK2−/−)
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Embryonic Lethality: Germline deletion of AK2 results in embryonic lethality at ~E7.5 due to severe mitochondrial ultrastructural defects, including disorganized cristae .
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Developmental Role: AK2 is indispensable for early embryogenesis, particularly during the formation of the first organ (the heart), where it regulates energy supply-demand balance .
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Mitochondrial Dysfunction: AK2−/− embryos exhibit disrupted mitochondrial architecture, highlighting its role in maintaining cristae integrity .
Cancer Metastasis
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Lung Adenocarcinoma: AK2 knockdown (AK2-KN) or knockout (AK2-KO) in human A549 lung cancer cells reduced migration and invasion in vitro and suppressed metastasis in nude mouse xenograft models .
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Mechanistic Insight: AK2 promotes epithelial-mesenchymal transition (EMT) by activating the TGF-β/Smad pathway. Loss of AK2 upregulated epithelial markers (e.g., E-cadherin) and downregulated mesenchymal markers (e.g., N-cadherin, Vimentin) .
| AK2 Knockout in Lung Cancer Models |
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| Phenotype |
| In vitro migration |
| In vivo metastasis |
| EMT Regulation |
While not murine, zebrafish AK2 mutants (e.g., ak2 del2/del2) replicate hematopoietic defects and apoptosis due to oxidative stress, mirroring findings in mice . These models highlight AK2’s conserved role in stress response and cell survival.
Unresolved Questions and Future Directions
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Compensatory Mechanisms: How do AK1, AK3, and AK4 compensate for AK2 loss in adult tissues?
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Therapeutic Targeting: Can AK2 inhibition be leveraged for cancer therapy without disrupting cardiac function?
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Developmental Pathways: What molecular signals link AK2 to mitochondrial cristae formation during embryogenesis?
Key Citations
Product Specs
Adenylate kinase 2 mitochondrial isoform a, Ak-2, D4Ertd220e, mitochondrial, ATP-AMP transphosphorylase 2, ATP:AMP phosphotransferas, Adenylate monophosphate kinase.
MGSSHHHHHH SSGLVPRGSH MGSHMAPNVL ASEPEIPKGI RAVLLGPPGA GKGTQAPKLA ENFCVCHLAT GDMLRAMVAS GSEL TMDAGKLVSD EMVVELIEKN LETPSCKNGF LLDGFPRTVR QAEMLDDLME KRKEKLDSVI EFSIQDSLLI RRITGRLIHP KSGRS
NPPKEPMKDD ITGEPLIRRS DDNEKALKTR LEAYHTQTTP LVEYYRKRGI HCAIDASQTP DIVFASILAA FSKATCKDLV MFI
Product Science Overview
In vertebrates, there are three main isoforms of adenylate kinase: AK1, AK2, and AK3. These isoforms are tissue-specific and developmentally regulated. AK2 is primarily localized in the mitochondrial intermembrane space and is involved in apoptosis . This localization is crucial for its role in maintaining the balance of adenine nucleotides within the mitochondria, which is essential for cellular energy metabolism and signaling.
The recombinant form of AK2 from mice is produced in Escherichia coli (E. coli). It is a single, non-glycosylated polypeptide chain containing 263 amino acids and has a molecular mass of approximately 29 kDa . The recombinant protein is often fused to a His-tag at the N-terminus to facilitate purification through chromatographic techniques.
Mutations in the AK2 gene are associated with reticular dysgenesis, a severe combined immunodeficiency characterized by a lack of white blood cells and sensorineural hearing loss . The enzyme’s role in apoptosis and energy metabolism makes it a potential target for therapeutic interventions in various diseases, including neurodegenerative disorders and metabolic syndromes .
