Citation | Phill Hawkins has made many outstanding contributions to knowledge of the variety and functions of inositol lipids and polyphosphates in eukaryotic cells, most of them jointly with his long-time collaborator Len Stephens. Discovery of Ins(3,4,5,6)P4 and pyrophosphorylated derivatives of InsP6 and proof that cells contain 3-phosphorylated derivatives of phosphatidylinositol (PtdIns) were early highlights. They then showed that PtdIns(4,5)P2 is the main substrate of receptorcontrolled phosphoinositide 3-kinases (PI3Ks), identifying PtdIns(3,4,5)P3 as a key signal in stimulated cells. They and Alessi (FRS 2008) discovered, in parallel, that phosphoinositidedependent kinase-1 (PDK1) is the PtdIns(3,4,5)P3-activated link between PI3K and protein kinase B, defining a key pathway through which PtdIns(3,4,5)P3 regulates cell proliferation and survival. Having identified and characterised the GPCR-activated Type 1B PI3K (PI3K) and explained its complex regulation by G and Ras-GTP, they used mutant mice to demonstrate the contributions of PI3K and other PI3K isoforms to inflammatory events in vivo. They have also: defined the pathway from PI3K activation, via Rac activation, to cytoskeletal reorganization; identified multiple PtdIns(3,4,5)P3 effectors; demonstrated that interaction between PtdIns3P and a protein PX domain is essential for activation of the bacteriocidal oxidase of neutrophils; and developed a sensitive MS-based assay for polyphosphoinositides in cell extracts. Following Len Stephens's election in 2011, it would be appropriate to elect his long-term and equal scientific partner. |