AKT1/AKT2/AKT3 Antibody

Overview of AKT1/AKT2/AKT3 Antibodies

AKT (Protein Kinase B) antibodies are specialized tools designed to detect and quantify the three AKT isoforms (AKT1, AKT2, AKT3) in biological samples. These serine-threonine kinases play critical roles in cellular processes such as proliferation, survival, and metabolism, with isoform-specific functions observed in immune regulation and cancer progression . Antibodies targeting AKT isoforms enable researchers to study their expression, activation states (e.g., phosphorylation at Ser473/Thr308), and tissue-specific roles.

Development and Specificity of AKT Isoform-Specific Antibodies

Antibodies against AKT isoforms are rigorously validated for specificity due to the high structural similarity (~80% homology) between isoforms. Key advancements include:

Table 1: Antibody Validation and Applications

Phospho-specific antibodies (e.g., pAKT Ser473) are widely used to assess activation status, though their ability to distinguish isoforms varies. For example, the pAKT2 Ser474 antibody shows weak cross-reactivity with AKT3 .

Cancer Biology

• Opposing roles in metastasis: AKT1 suppresses breast cancer migration, while AKT2 promotes it .

• Lineage-specific activation: AKT2 drives survival in PTEN-deficient prostate cancer, whereas AKT1 mutations (e.g., E17K) are more common in hematologic malignancies .

• Quantitative assays: Reverse-phase protein arrays (RPPA) using isoform-specific antibodies revealed AKT1 is predominant in luminal breast cancer, while AKT3 is upregulated in basal subtypes .

Immune System Regulation

• Lymphocyte signaling: AKT1 is critical for TCR-induced mTOR activation and NFAT signaling, detected via nuclear translocation assays .

• Developmental redundancy: Mice lacking AKT2/AKT3 survive with minimal dysfunction, but show glucose intolerance and reduced brain/testis size, highlighting AKT1's sufficiency for basic development .

Technical Considerations for AKT Antibody Use

• Sensitivity: NanoPro 1000 assays enable AKT phosphoform detection from as few as 56 cells .

• Isoform discrimination:

  • pI differences: AKT1 (pI 5.46–5.63) and AKT2 (pI 5.75–6.04) can be separated via isoelectric focusing .

  • Phosphorylation status: pAKT Ser473 antibodies primarily detect AKT1 in breast cancer models .

Clinical and Therapeutic Implications

AKT isoform-specific antibodies are pivotal for:

• Biomarker discovery: Elevated pAKT1 Ser473 correlates with PI3K pathway activation in tumors .

• Drug development: Isoform-selective inhibitors (e.g., AKT1 vs. AKT2) are being tested to minimize toxicity .