Oncogenic kinase signalling

Protein-tyrosine kinases (PTKs) are important regulators of intracellular s ignal-transduction pathways mediating development and multicellular communi cation in metazoans. Their activity is normally tightly controlled and regu lated. Perturbation of PTK signalling by mutations and other genetic altera tions results in deregulated kinase activity and malignant transformation. The lipid kinase phosphoinositide 3-OH kinase (PI(3)K) and some of its down stream targets, such as the protein-serine/threonine kinases Akt and p70 S6 kinase (p70(S6K)), are crucial effectors in oncogenic PTK signalling. This review emphasizes how oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity a nd provides an update on our knowledge about the role of deregulated PI(3)K /Akt and mammalian target of rapamycin/p70(S6K) signalling in human maligna ncies.