Multi-Isoform AKT Signaling: A Systems-Level Analysis of Cellular Homeostasis and Oncogenesis
: Predominantly expressed in the brain, where it regulates organ size and neurodevelopment. 3. Pathological Dysregulation 3.1 Cancer File: AKT_collection_compressed_2022-11-20.zip ...
Research indicates that AKT isoforms are not functionally redundant: This paper analyzes the distinct and overlapping roles
AKT (Protein Kinase B) is a critical serine-threonine kinase existing in three isoforms (AKT1, AKT2, AKT3) that integrates signals from the PI3K pathway to regulate metabolism, survival, and proliferation. This paper analyzes the distinct and overlapping roles of these isoforms using transcriptomic landscapes and multi-omic profiling. We demonstrate that while AKT1 primarily drives somatic growth, AKT2 is essential for glucose metabolism, and AKT3 influences neuronal development. Furthermore, we explore how aberrant activation via somatic mutations, such as AKT1 (E17K), contributes to tumorigenesis in breast and colorectal cancers. 1. Introduction AKT2 is essential for glucose metabolism
The PI3K/AKT/mTOR signaling axis is one of the most frequently dysregulated pathways in human disease. AKT acts as a central hub, receiving signals from receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs). Upon recruitment to the plasma membrane via its PH domain, AKT is activated by phosphorylation at T308 and S473. 2. Isoform-Specific Functions
: The primary regulator of insulin-dependent glucose uptake in muscle and adipose tissue.