The protein kinase B/Akt signalling pathway in human malignancy

Protein kinase B or Akt (PKB.Akt) is a serine threonine kinase. which in mammals comprises three highly homologous members known as PKBalpha (Akt1). PKB3 (Akt2). Laid PKBgamma (Akt3). PKB Akt is activated in cells exposed to diverse stimuli such as hormones. growth factors, and extracellular Matrix components. The actuation mechanism remains to be fully characterised but occurs downstream of phosphoinositide 3-kinase (PI-3K). PI-3K generate, phosphatidylinositol-3,4,5-trisphosphate (PIP3), a lipid second messenger essential for the translocation of PKB.Akt to the plasma membrane where it is phosphorylated and activated by phosphoinositide-dependent kinase-l (PDK-1) and possibly other kinases. PKB.Akt phosphorylate and regulates the function of many cellular proteins in coked in processes that include metabolism, apoptosis, and proliferation. Recent evidence indicates that PKB Akt is frequently constitutively active in many types of human cancer. Constitutive PKB Akt activation can occur due to amplification of PKB.Akt genes or as a result of mutations in components of the signalling pathway that activates PKB.Akt. Although the mechanisms have not yet been Puny characterised, constitutive PKB.Akt signalling is believed to promote proliferation and increased cell survival and thereby contributing to cancer progression. This review surveys recent de developments in understanding the mechanisms and consequences of PKB.Akt activation in human malignancy. (C) 2002 Elsevier Science Ire. All rights reserved.