Phosphoinositide 3-kinase: a key biochemical signal for cell migration in response to chemokines

Chemokines can couple to distinct signalling pathways that have been demons trated to mediate not only migration, but also cell growth and transcriptio nal activation. One particular signalling pathway, namely that controlled b y the lipid kinase phosphoinositide 3-kinase (PI3K), has been the focus of much attention with respect to its activation by chemokine receptors and th e role it plays in regulating cell migration. Identification of PI3K is arg uably one of the most exciting recent developments in biochemical signallin g. Pharmacological and genetic studies have now convincingly shown that bot h CC and CXC chemokines stimulate PI3K-dependent chemotaxis of inflammatory cells such as eosinophils, macrophages, neutrophils and T lymphocytes. Thi s review considers the role of specific sub-classes of PI3Ks (e.g. the p85/ p110 heterodimer, PI3K gamma and PI3K-C2 alpha) as well as their downstream effector targets in mediating chemokine-stimulated cell migration.