Protein kinase B (Akt)

Protein kinase B (Akt), often referred to as PKB or by its individual isoforms Akt1, Akt2, and Akt3, is a family of serine/threonine kinases that serves as a critical regulator of cell survival, metabolism, growth, proliferation, and migration[1][3][6][9][12]. Akt is activated via the phosphoinositide 3-kinase (PI3K) signaling pathway, typically in response to growth factors, insulin, and other extracellular stimuli, and transduces signals that suppress apoptosis and promote cellular growth[1][3][6][9]. Isoform-specific functions include regulation of glucose homeostasis (Akt2), brain development (Akt3), and general growth and anti-apoptosis (Akt1). Dysregulation or mutation of Akt, especially activating mutations or pathway amplification, is frequently implicated in human diseases including multiple cancer types, diabetes, inflammatory disorders, and overgrowth syndromes[3][4][6][9]. Due to its central signaling role, Akt is a validated therapeutic target, though drugs that inhibit its activity face challenges including resistance, off-target toxicity, and the need for predictive biomarkers for optimal patient selection[2][4][6].

Other names

AktPKBAKT serine/threonine kinaseRAC-alpha serine/threonine-protein kinase (for AKT1 specifically)PKB alpha, PKB beta, PKB gamma (for isoforms)Protein kinase B alpha (Akt1), Protein kinase B beta (Akt2), Protein kinase B gamma (Akt3)

ATP-competitive inhibition (binds to the ATP-binding pocket and inhibits kinase activity); Allosteric inhibition (binds to a site distinct from the ATP pocket and stabilizes inactive conformation); Covalent-allosteric inhibition (irreversibly modifies noncatalytic cysteine residues, increasing selectivity and potency); Disruption of PH domain-PIP3 interaction (inhibits membrane recruitment/activation)