Dr Phillip Hawkins FRS
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 receptor-controlled 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 phosphoinositide-dependent 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 (PI3Kγ) and explained its complex regulation by Gβγ and Ras-GTP, they used mutant mice to demonstrate the contributions of PI3Kγ 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.
■The regulation of cell function by a family of inositol-containing phospholipids