Liver kinase B1–AMP-activated protein kinase signaling pathway (LKB1–AMPK pathway)

The Liver kinase B1 (LKB1)–AMP-activated protein kinase (AMPK) signaling pathway is a fundamental regulator of cellular energy homeostasis and metabolic health [1]. LKB1, a serine/threonine kinase encoded by the STK11 gene, serves as the primary upstream activator of AMPK by phosphorylating its alpha subunit at the Threonine-172 residue in response to energy stress or decreased ATP levels [2]. Once activated, AMPK acts as a metabolic master switch that restores energy balance by promoting catabolic pathways, such as fatty acid oxidation and glucose uptake, while simultaneously inhibiting anabolic processes like protein and lipid synthesis [3][4]. This pathway is critical for maintaining insulin sensitivity and suppressing tumor growth, making it a significant focus for therapeutic intervention in type 2 diabetes and various malignancies [5]. While drugs like metformin activate this pathway indirectly by altering the cellular energy state, newer direct AMPK activators are being developed to treat metabolic and cardiovascular diseases [6]. However, the pathway's role in oncology is complex; while it generally acts as a tumor suppressor, it may also support the survival of established cancer cells under extreme nutrient deprivation [7].

Other names

LKB1-AMPK axisSTK11-AMPK pathwayAMPK signaling cascade

Activation of AMPK through phosphorylation by LKB1 or direct allosteric binding to the AMPK complex to stimulate ATP-producing pathways and inhibit ATP-consuming pathways.