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

Sotsios, Yannis
Ward, Stephen G.

Authors' address Yannis Sotsios, Stephen G. Ward, Department of Pharmacy and Pharmacology, Bath University, Claverton Down, Bath, Avon, UK.

Correspondence to: Stephen G. Ward; Department of Pharmacy and Pharmacology; Bath University; Claverton Down; Bath; Avon BA2 7A4; UK; Fax: 44 1225 826114; e-mail: [email protected]

Acknowledgements The authors thank Sarah Turner, Marisa Logan and Gill Whittaker for their carefully conceived and meticulous experiments characterising chemokine signal transduction pathways. S. G. W. is supported by the Wellcome Trust.

Immunological Reviews 177:p 217-235, October 2000.

Summary:

Chemokines can couple to distinct signalling pathways that have been demonstrated to mediate not only migration, but also cell growth and transcriptional activation. One particular signalling pathway, namely that controlled by the lipid kinase phosphoinositide 3-kinase (PI3K), has been the focus of much attention with respect to its activation by chemokine receptors and the role it plays in regulating cell migration. Identification of PI3K is arguably one of the most exciting recent developments in biochemical signalling. Pharmacological and genetic studies have now convincingly shown that both CC and CXC chemokines stimulate PI3K-dependent chemotaxis of inflammatory cells such as eosinophils, macrophages, neutrophils and T lymphocytes. This review considers the role of specific sub-classes of PI3Ks (e.g. the p85/p110 heterodimer, PI3Kγ and PI3K-C2α) as well as their downstream effector targets in mediating chemokine-stimulated cell migration.