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RefNoEC/2011/39
LevelItem
TitleStephens, Leonard Robert: certificate of election to the Royal Society
Date19 May 2011
DescriptionCertificate of Election
CitationIn joint studies with his long-time collaborator Phill Hawkins, Len Stephens has made many outstanding contributions to knowledge of the variety and functions of inositol lipids and polyphosphates in eukaryotic cells. Early highlights were the mapping of new pathways of inositol phosphate synthesis, discovery of Ins(3,4,5,6)P4 and pyrophosphorylated derivatives of InsP6, and structural proof that cells contain 3-phosphorylated derivatives of phosphatidylinositol (PtdIns) - the analytical methods they developed for these studies are now standard. They 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 from this reaction. They identified and isolated the GPCR-activated Type 1B PI3K (PI3K?) and, in a sustained body of work, defined its structure, explained its complex pattern of regulation by G?? and Ras, and proved its role in inflammatory events in vivo. They - in parallel with Alessi, FRS 2008 - 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.
[Crossed out on citation in certificate: 'Other major contributions have included: definition of the pathway from PI3K-1 activation, via ARAP3 and Rac activation, to cytoskeletal reorganization; development of a proteomic screen with which they identified several PtdIns(3,4,5)P3 effectors; demonstration that a PtdIns3P:PX domain interaction is a key event in activation of the bacteriocidal oxidase of neutrophils; and explanation, using genetically engineered mice, how 3-phosphoinositides make essential contributions to inflammatory and microbicidal events in neutrophils. ']
Extent4p
FormatPrinted
AccessStatusClosed
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