Phill Hawkins has contributed much to the understanding of inositol lipids functions in eukaryotic cells. Together with his long-time collaborator Leonard R Stephens, he established that PtdIns(4,5)P2 is the main substrate of receptor-controlled Type 1 phosphoinositide 3-kinases (PI3Ks), thus identifying PtdIns(3,4,5)P3 as the key output signal produced by this enzyme.[2]
They identified and isolated the GPCR-activated Type 1B PI3K (PI3KΥ) and, in a sustained body of work, defined its structure, explained its complex pattern of regulation by GβΥ and Ras, and proved its role in inflammatory eventsin vivo.[3] They - in parallel with Dario Alessi - identified phosphoinositide-dependent kinase-1 as the PtdIns(3,4,5)P3-activated link between PI3K-1 activation and protein kinase B activation, a key pathway through which PtdIns(3,4,5)P3 formation regulates cell proliferation and survival.[4][5]
^P.T. Hawkins, T.R. Jackson, L.R. Stephens (1992) Platelet-derived growth factor stimulates synthesis of Ptdlns(3,4,5)P3 by activating a Ptdlns(4,5)P2 3-OH kinase. Nature358, 157-159
^L. Stephens, A. Smrcka, F.T. Cooke, T.R. Jackson, P.C. Sternweis, P.T. Hawkins (1994) A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated by G protein βγ subunits. Cell77, 83-93
^David Stokoe, Leonard R. Stephens, Terry Copeland, Piers R. J. Gaffney, Colin B. Reese, Gavin F. Painter, Andrew B. Holmes, Frank McCormick, Phillip T. Hawkins (1997) Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B. Science277, 567-570
^Len Stephens, Karen Anderson, David Stokoe, Hediye Erdjument-Bromage, Gavin F. Painter, Andrew B. Holmes, Piers R.J. Gaffney, Colin B. Reese, Frank McCormick, Paul Tempst, J. Coadwell, Phillip T. Hawkins (1998) Protein Kinase B Kinases That Mediate Phosphatidylinositol 3,4,5-Trisphosphate-Dependent Activation of Protein Kinase B. Science279, 710-714