AKTsignaalin

AKTsignaalin, commonly referred to as the AKT signaling pathway, is a central signal transduction pathway that regulates cell survival, growth, metabolism, and proliferation. It centers on the serine/threonine kinase Akt, also known as protein kinase B (PKB). Akt is activated downstream of phosphoinositide 3-kinase (PI3K) triggered by growth factors, insulin, and other extracellular cues. PI3K generates PIP3 at the plasma membrane, recruiting Akt via its PH domain. Activation requires phosphorylation at Thr308 by PDK1 and at Ser473 by mTORC2, leading to full kinase activity. Once active, AKT phosphorylates a range of substrates, including BAD (inhibiting apoptosis), FOXO transcription factors (nuclear exclusion), GSK3, and TSC2, which relieves inhibition of mTORC1 and promotes protein synthesis and growth. The pathway also modulates glucose uptake and metabolism, lipid synthesis, and cell cycle progression.

Regulation is tightly controlled; PTEN and SHIP phosphatases limit PIP3 signaling, while PHLPP phosphatases terminate AKT signaling by dephosphorylating Ser473. There are three Akt isoforms (Akt1, Akt2, Akt3) with overlapping but distinct tissue distributions and roles.

Dysregulation of AKT signaling is linked to cancer, metabolic diseases, and neurodegeneration. Hyperactivation can result from PI3K mutations, PTEN loss, or amplifications, making AKT a target for therapeutic inhibitors, several of which are in clinical development or use. Diagnostic and research tools often rely on detecting phosphorylated Akt as a marker of pathway activity.